Patent Publication Number: US-2022233444-A1

Title: Thioester cationic lipids

Description:
RELATED APPLICATIONS 
     This application claims priority to U.S. Provisional Application Ser. No. 62/836,930, filed on Apr. 22, 2019, the entire disclosure of which is hereby incorporated by reference. 
    
    
     BACKGROUND 
     Delivery of nucleic acids has been explored extensively as a potential therapeutic option for certain disease states. In particular, messenger RNA (mRNA) therapy has become an increasingly important option for treatment of various diseases, including for those associated with deficiency of one or more proteins. 
     SUMMARY 
     The present invention provides, among other things, a novel class of thioester cationic lipid compounds for improved in vivo delivery of therapeutic agents, such as nucleic acids. It is contemplated that the compounds provided herein are capable of highly effective in vivo delivery while maintaining a favorable toxicity profile. 
     In an aspect, provided herein are cationic lipids having a structure according to Formula (A), 
     
       
         
         
             
             
         
       
     
     or a pharmaceutically acceptable salt thereof, wherein 
     each R 1  is independently C 6 -C 33  aliphatic; 
     L 1  is independently —(CR 2a R 2b ) a —, —(CH 2 CH 2 S) b CH 2 CH 2 —, or —CH 2 CH 2 (OCH 2 CH 2 ) c —; 
     each R 2a  and R 2b  is independently hydrogen or C 1 -C 6  alkyl; 
     each n is independently an integer of 0-12; 
     each a is independently an integer of 1-12; 
     each b is independently an integer of 1-11; and 
     each c is independently an integer of 1-11. 
     In embodiments, each R 2a  and R 2b  is independently hydrogen or methyl. 
     In embodiments, each L 1  is independently —(CH 2 ) a —, —(CHCH 3 ) a —, —(CH 2 CH 2 S) b CH 2 CH 2 —, or —CH 2 CH 2 (OCH 2 CH 2 ) c —. 
     In embodiments, L 1  is —(CH 2 ) a —. 
     In embodiments, a cationic lipid has the following structure: 
     
       
         
         
             
             
         
       
     
     or a pharmaceutically acceptable salt thereof. 
     In embodiments, a cationic lipid has the following structure: 
     
       
         
         
             
             
         
       
     
     or a pharmaceutically acceptable salt thereof. 
     In embodiments, a cationic lipid has the following structure: 
     
       
         
         
             
             
         
       
     
     or a pharmaceutically acceptable salt thereof. 
     In embodiments, L 1  is —(CHCH 3 ) a —, 
     In embodiments, a cationic lipid has the following structure: 
     
       
         
         
             
             
         
       
     
     or a pharmaceutically acceptable salt thereof. 
     In embodiments, a cationic lipid has the following structure: 
     
       
         
         
             
             
         
       
     
     or a pharmaceutically acceptable salt thereof. 
     In embodiments, L 1  is —(CH 2 CH 2 S) b CH 2 CH 2 —, and b is 1, 2, 3, 4, or 5. 
     In embodiments, a cationic lipid has the following structure: 
     
       
         
         
             
             
         
       
     
     or a pharmaceutically acceptable salt thereof. 
     In embodiments, L 1  is —CH 2 CH 2 (OCH 2 CH 2 ) c —, and c is 1, 2, 3, 4, or 5. 
     In embodiments, a cationic lipid has the following structure: 
     
       
         
         
             
             
         
       
     
     or a pharmaceutically acceptable salt thereof. 
     In embodiments, each R 1  is C 6 -C 24  alkyl. 
     In embodiments, each R 1  is C 8 H 17 , C 10 H 21 , or C 12 H 25 . 
     In embodiments, each R 1  is C 6 -C 24  alkenyl. 
     In embodiments, each R 1  is C 6 -C 24  alkynyl. 
     In embodiments, n is 1, 2, 3, or 4. 
     In embodiments, a cationic lipid is any one of Compounds 1-63. 
     In another aspect, the invention features a composition comprising any liposome (e.g., a liposome encapsulating an mRNA encoding a protein) described herein. In embodiments, the liposome comprises a cationic lipid described herein. 
     In embodiments, an mRNA encodes for cystic fibrosis transmembrane conductance regulator (CFTR) protein. 
     In embodiments, an mRNA encodes for ornithine transcarbamylase (OTC) protein. 
     In another aspect, the invention features a composition comprising a nucleic acid encapsulated within a liposome as described herein. In embodiments, the liposome comprises a cationic lipid described herein. 
     In embodiments, a composition further comprises one more lipids selected from the group consisting of one or more cationic lipids, one or more non-cationic lipids, and one or more PEG-modified lipids. 
     In embodiments, a nucleic acid is an mRNA encoding a peptide or protein. 
     In embodiments, an mRNA encodes a peptide or protein for use in the delivery to or treatment of the lung of a subject or a lung cell. 
     In embodiments, an mRNA encodes a peptide or protein for use in the delivery to or treatment of the lung of a subject or a lung cell. 
     In embodiments, an mRNA encodes for cystic fibrosis transmembrane conductance regulator (CFTR) protein. 
     In embodiments, an mRNA encodes a peptide or protein for use in the delivery to or treatment of the liver of a subject or a liver cell. 
     In embodiments, an mRNA encodes for ornithine transcarbamylase (OTC) protein. 
     In embodiments, an mRNA encodes a peptide or protein for use in vaccine. 
     In embodiments, an mRNA encodes an antigen. 
     in some aspects, the present invention provides methods of treating a disease in a subject comprising administering to the subject a composition as described herein. 
    
    
     
       BRIEF DESCRIPTION OF DRAWINGS 
         FIG. 1  depicts in vivo protein production resulting from the delivery of mRNA using lipid nanoparticles comprising Compound 30 as described herein. As shown in this Figure, use of this compound allows high levels of in vivo protein production even 6 hours after administration. 
     
    
    
     DETAILED DESCRIPTION OF CERTAIN EMBODIMENTS 
     Definitions 
     In order for the present invention to be more readily understood, certain terms are first defined below. Additional definitions for the following terms and other terms are set forth throughout the specification. The publications and other reference materials referenced herein to describe the background of the invention and to provide additional detail regarding its practice are hereby incorporated by reference. 
     Amino acid: As used herein, the term “amino acid,” in its broadest sense, refers to any compound and/or substance that can be incorporated into a polypeptide chain. In some embodiments, an amino acid has the general structure H 2 N—C(H)(R)—COOH. In some embodiments, an amino acid is a naturally occurring amino acid. In some embodiments, an amino acid is a synthetic amino acid; in some embodiments, an amino acid is a d-amino acid; in some embodiments, an amino acid is an I-amino acid. “Standard amino acid” refers to any of the twenty standard I-amino acids commonly found in naturally occurring peptides. “Nonstandard amino acid” refers to any amino acid, other than the standard amino acids, regardless of whether it is prepared synthetically or obtained from a natural source. As used herein, “synthetic amino acid” encompasses chemically modified amino acids, including but not limited to salts, amino acid derivatives (such as amides), and/or substitutions. Amino acids, including carboxy- and/or amino-terminal amino acids in peptides, can be modified by methylation, amidation, acetylation, protecting groups, and/or substitution with other chemical groups that can change the peptide&#39;s circulating half-life without adversely affecting their activity. Amino acids may participate in a disulfide bond. Amino acids may comprise one or posttranslational modifications, such as association with one or more chemical entities (e.g., methyl groups, acetate groups, acetyl groups, phosphate groups, formyl moieties, isoprenoid groups, sulfate groups, polyethylene glycol moieties, lipid moieties, carbohydrate moieties, biotin moieties, etc.). The term “amino acid” is used interchangeably with “amino acid residue,” and may refer to a free amino acid and/or to an amino acid residue of a peptide. It will be apparent from the context in which the term is used whether it refers to a free amino acid or a residue of a peptide. 
     Animal: As used herein, the term “animal” refers to any member of the animal kingdom. In some embodiments, “animal” refers to humans, at any stage of development. In some embodiments, “animal” refers to non-human animals, at any stage of development. In certain embodiments, the non-human animal is a mammal (e.g., a rodent, a mouse, a rat, a rabbit, a monkey, a dog, a cat, a sheep, a bovine, a primate, and/or a pig). In some embodiments, animals include, but are not limited to, mammals, birds, reptiles, amphibians, fish, insects, and/or worms. In some embodiments, an animal may be a transgenic animal, genetically-engineered animal, and/or a clone. 
     Approximately or about: As used herein, the term “approximately” or “about,” as applied to one or more values of interest, refers to a value that is similar to a stated reference value. In certain embodiments, the term “approximately” or “about” refers to a range of values that fall within 25%, 20%, 19%, 18%, 17%, 16%, 15%, 14%, 13%, 12%, 11%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, or less in either direction (greater than or less than) of the stated reference value unless otherwise stated or otherwise evident from the context (except where such number would exceed 100% of a possible value). 
     Biologically active: As used herein, the term “biologically active” refers to a characteristic of any agent that has activity in a biological system, and particularly in an organism. For instance, an agent that, when administered to an organism, has a biological effect on that organism, is considered to be biologically active. 
     Delivery: As used herein, the term “delivery” encompasses both local and systemic delivery. For example, delivery of mRNA encompasses situations in which an mRNA is delivered to a target tissue and the encoded protein is expressed and retained within the target tissue (also referred to as “local distribution” or “local delivery”), and situations in which an mRNA is delivered to a target tissue and the encoded protein is expressed and secreted into patient&#39;s circulation system (e.g., serum) and systematically distributed and taken up by other tissues (also referred to as “systemic distribution” or “systemic delivery”). 
     Expression: As used herein, “expression” of a nucleic acid sequence refers to translation of an mRNA into a polypeptide, assemble multiple polypeptides into an intact protein (e.g., enzyme) and/or post-translational modification of a polypeptide or fully assembled protein (e.g., enzyme). In this application, the terms “expression” and “production,” and grammatical equivalents thereof, are used interchangeably. 
     Functional: As used herein, a “functional” biological molecule is a biological molecule in a form in which it exhibits a property and/or activity by which it is characterized. 
     Half-life: As used herein, the term “half-life” is the time required for a quantity such as nucleic acid or protein concentration or activity to fall to half of its value as measured at the beginning of a time period, 
     Helper lipid: The term “helper lipid” as used herein refers to any neutral or zwitterionic lipid material including cholesterol, Without wishing to be held to a particular theory, helper lipids may add stability, rigidity, and/or fluidity within lipid bilayers/nanoparticles. 
     Improve, increase, or reduce: As used herein, the terms “improve,” “increase,” or “reduce,” or grammatical equivalents, indicate values that are relative to a baseline measurement, such as a measurement in the same individual prior to initiation of the treatment described herein, or a measurement in a control subject (or multiple control subject) in the absence of the treatment described herein. A “control subject” is a subject afflicted with the same form of disease as the subject being treated, who is about the same age as the subject being treated. 
     In Vitro: As used herein, the term “in vitro” refers to events that occur in an artificial environment, e.g., in a test tube or reaction vessel, in cell culture, etc., rather than within a multi-cellular organism. 
     In Vivo: As used herein, the term “in vivo” refers to events that occur within a multi-cellular organism, such as a human and a non-human animal. In the context of cell-based systems, the term may be used to refer to events that occur within a living cell (as opposed to, for example, in vitro systems) 
     Isolated: As used herein, the term “isolated” refers to a substance and/or entity that has been (1) separated from at least some of the components with which it was associated when initially produced (whether in nature and/or in an experimental setting), and/or (2) produced, prepared, and/or manufactured by the hand of man, isolated substances and/or entities may be separated from about 10%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, about 80%, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99%, or more than about 99% of the other components with which they were initially associated. In some embodiments, isolated agents are about 80%, about 85%, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99%, or more than about 99% pure. As used herein, a substance is “pure” if it is substantially free of other components. As used herein, calculation of percent purity of isolated substances and/or entities should not include excipients (e.g., buffer, solvent, water, etc.). 
     Liposome: As used herein, the term “liposome” refers to any lamellar, multilamellar, or solid nanoparticle vesicle. Typically, a liposome as used herein can be formed by mixing one or more lipids or by mixing one or more lipids and polymer(s). In some embodiments, a liposome suitable for the present invention contains a cationic lipids(s) and optionally non-cationic lipid(s), optionally cholesterol-based lipid(s), and/or optionally PEG-modified lipid(s). 
     messenger RNA (mRNA): As used herein, the term “messenger RNA (mRNA)” or “mRNA” refers to a polynucleotide that encodes at least one polypeptide. mRNA as used herein encompasses both modified and unmodified RNA. The term “modified mRNA” related to mRNA comprising at least one chemically modified nucleotide, mRNA may contain one or more coding and non-coding regions. mRNA can be purified from natural sources, produced using recombinant expression systems and optionally purified, chemically synthesized, etc. Where appropriate, e.g., in the case of chemically synthesized molecules, mRNA can comprise nucleoside analogs such as analogs having chemically modified bases or sugars, backbone modifications, etc. An mRNA sequence is presented in the 5′ to 3′ direction unless otherwise indicated. In some embodiments, an mRNA is or comprises natural nucleosides (e.g., adenosine, guanosine, cytidine, uridine); nucleoside analogs (e.g., 2-aminoadenosine, 2-thiothymidine, inosine, pyrrolo-pyrimidine, 3-methyl adenosine, 5-methylcytidine, C-5 propynyl-cytidine, C-5 propynyl-uridine, 2-aminoadenosine, C5-bromouridine, C5-fluorouridine, C5-iodouridine, C5-propynyl-uridine, C5-propynyl-cytidine, C5-methylcytidine, 2-aminoadenosine, 7-deazaadenosine, 7-deazaguanosine, 8-oxoadenosine, 8-oxoguanosine, O(6)-methylguanine, and 2-thiocytidine); chemically modified bases; biologically modified bases (e.g., methylated bases); intercalated bases; modified sugars (e.g., 2′-fluororibose, ribose, 2′-deoxyribose, arabinose, and hexose); and/or modified phosphate groups (e.g., phosphorothioates and 5′-N-phosphoramidite linkages). 
     Nucleic acid: As used herein, the term “nucleic acid,” in its broadest sense, refers to any compound and/or substance that is or can be incorporated into a polynucleotide chain. In some embodiments, a nucleic acid is a compound and/or substance that is or can be incorporated into a polynucleotide chain via a phosphodiester linkage. In some embodiments, “nucleic acid” refers to individual nucleic acid residues (e.g., nucleotides and/or nucleosides). In some embodiments, “nucleic acid” refers to a polynucleotide chain comprising individual nucleic acid residues. In some embodiments, “nucleic acid” encompasses RNA as well as single and/or double-stranded DNA and/or cDNA. In some embodiments, “nucleic acid” encompasses ribonucleic acids (RNA), including but not limited to any one or more of interference RNAs (RNAi), small interfering RNA (siRNA), short hairpin RNA (shRNA), antisense RNA (aRNA), messenger RNA (mRNA), modified messenger RNA (mmRNA), long non-coding RNA (lncRNA), micro-RNA (miRNA) multimeric coding nucleic acid (MCNA), polymeric coding nucleic acid (PCNA), guide RNA (gRNA) and CRISPR RNA (crRNA). In some embodiments, “nucleic acid” encompasses deoxyribonucleic acid (DNA), including but not limited to any one or more of single-stranded DNA (ssDNA), double-stranded DNA (dsDNA) and complementary DNA (cDNA). In some embodiments, “nucleic acid” encompasses both RNA and DNA. In embodiments, DNA may be in the form of antisense DNA, plasmid DNA, parts of a plasmid DNA, pre-condensed DNA, a product of a polymerase chain reaction (PCR), vectors (e.g., P1, PAC, BAC, YAC, artificial chromosomes), expression cassettes, chimeric sequences, chromosomal DNA, or derivatives of these groups. In embodiments, RNA may be in the form of messenger RNA (mRNA), ribosomal RNA (rRNA), signal recognition particle RNA (7 SL RNA or SRP RNA), transfer RNA (tRNA), transfer-messenger RNA (tmRNA), small nuclear RNA (snRNA), small nucleolar RNA (snoRNA), SmY RNA, small Cajal body-specific RNA (scaRNA), guide RNA (gRNA), ribonuclease P (RNase P), Y RNA, telomerase RNA component (TERC), spliced leader RNA (SL RNA), antisense RNA (aRNA or asRNA), cis-natural antisense transcript (cis-NAT), CRISPR RNA (crRNA), long noncoding RNA (lncRNA), micro-RNA (miRNA), piwi-interacting RNA (piRNA), small interfering RNA (siRNA), transacting siRNA (tasiRNA), repeat associated siRNA (rasiRNA), 73K RNA, retrotransposons, a viral genome, a viroid, satellite RNA, or derivatives of these groups. In some embodiments, a nucleic acid is a mRNA encoding a protein such as an enzyme. 
     Patient: As used herein, the term “patient” or “subject” refers to any organism to which a provided composition may be administered, e.g., for experimental, diagnostic, prophylactic, cosmetic, and/or therapeutic purposes. Typical patients include animals (e.g., mammals such as mice, rats, rabbits, non-human primates, and/or humans). In some embodiments, a patient is a human. A human includes pre- and post-natal forms. 
     Pharmaceutically acceptable: The term “pharmaceutically acceptable,” as used herein, refers to substances that, within the scope of sound medical judgment, are suitable for use in contact with the tissues of human beings and animals without excessive toxicity, irritation, allergic response, or other problem or complication, commensurate with a reasonable benefit/risk ratio. 
     Pharmaceutically acceptable salt: Pharmaceutically acceptable salts are well known in the art. For example, S. M. Berge et al., describes pharmaceutically acceptable salts in detail in  J. Pharmaceutical Sciences  (1977) 66:1-19. Pharmaceutically acceptable salts of the compounds of this invention include those derived from suitable inorganic and organic acids and bases. Examples of pharmaceutically acceptable, nontoxic acid addition salts are salts of an amino group formed with inorganic acids such as hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid, and perchloric acid or with organic acids such as acetic acid, oxalic acid, maleic acid, tartaric acid, citric acid, succinic acid, or malonic acid, or by using other methods used in the art such as ion exchange. Other pharmaceutically acceptable salts include adipate, alginate, ascorbate, aspartate, benzenesulfonate, benzoate, bisulfate, borate, butyrate, camphorate, camphorsulfonate, citrate, cyclopentanepropionate, digluconate, dodecylsulfate, ethanesulfonate, formate, fumarase, glucoheptonate, glycerophosphate, gluconate, hemisulfate, heptanoate, hexanoate, hydroiodide, 2-hydroxy-ethanesulfonate, lactobionate, lactate, laurate, lauryl sulfate, malate, maleate, malonate, methanesulfonate, 2-naphthalenesulfonate, nicotinate, nitrate, oleate, oxalate, palmitate, pamoate, pectinate, persulfate, 3-phenylpropionate, phosphate, picrate, pivalate, propionate, stearate, succinate, sulfate, tartrate, thiocyanate, p-toluenesulfonate, undecanoate, valerate salts, and the like. Salts derived from appropriate bases include alkali metal, alkaline earth metal, ammonium and N + (C 1-4  alkyl) 4  salts. Representative alkali or alkaline earth metal salts include sodium, lithium, potassium, calcium, magnesium, and the like. Further pharmaceutically acceptable salts include, when appropriate, nontoxic ammonium, quaternary ammonium, and amine cations formed using counterions such as halide, hydroxide, carboxylate, sulfate, phosphate, nitrate, sulfonate, and aryl sulfonate. Further pharmaceutically acceptable salts include salts formed from the quarternization of an amine using an appropriate electrophile, e.g., an alkyl halide, to form a quarternized alkylated amino salt. 
     Systemic distribution or delivery: As used herein, the terms “systemic distribution” or “systemic delivery,” or grammatical equivalents thereof, refer to a delivery or distribution mechanism or approach that affect the entire body or an entire organism. Typically, systemic distribution or delivery is accomplished via body&#39;s circulation system, e.g., blood stream. Compared to the definition of “local distribution or delivery.” 
     Subject: As used herein, the term “subject” refers to a human or any non-human animal (e.g., mouse, rat, rabbit, dog, cat, cattle, swine, sheep, horse or primate). A human includes pre- and post-natal forms, in many embodiments, a subject is a human being. A subject can be a patient, which refers to a human presenting to a medical provider for diagnosis or treatment of a disease. The term “subject” is used herein interchangeably with “individual” or “patient.” A subject can be afflicted with or is susceptible to a disease or disorder but may or may not display symptoms of the disease or disorder. 
     Substantially: As used herein, the term “substantially” refers to the qualitative condition of exhibiting total or near-total extent or degree of a characteristic or property cf interest. One of ordinary skill in the biological arts will understand that biological and chemical phenomena rarely, if ever, go to completion and/or proceed to completeness or achieve or avoid an absolute result. The term “substantially” is therefore used herein to capture the potential lack of completeness inherent in many biological and chemical phenomena. 
     Target tissues: As used herein, the term “target tissues” refers to any tissue that is affected by a disease to be treated. In some embodiments, target tissues include those tissues that display disease-associated pathology, symptom, or feature. 
     Therapeutically effective amount: As used herein, the term “therapeutically effective amount” of a therapeutic agent means an amount that is sufficient, when administered to a subject suffering from or susceptible to a disease, disorder, and/or condition, to treat, diagnose, prevent, and/or delay the onset of the symptom(s) of the disease, disorder, and/or condition. It will be appreciated by those of ordinary skill in the art that a therapeutically effective amount is typically administered via a dosing regimen comprising at least one unit dose. 
     Treating: As used herein, the term “treat,” “treatment,” or “treating” refers to any method used to partially or completely alleviate, ameliorate, relieve, inhibit, prevent, delay onset of, reduce severity of and/or reduce incidence of one or more symptoms or features of a particular disease, disorder, and/or condition. Treatment may be administered to a subject who does not exhibit signs cf a disease and/or exhibits only early signs of the disease for the purpose of decreasing the risk of developing pathology associated with the disease. 
     Aliphatic: As used herein, the term aliphatic refers to C 1 -C 40  hydrocarbons and includes both saturated and unsaturated hydrocarbons. An aliphatic may be linear, branched, or cyclic. For example, C 1 -C 20  aliphatics can include C 1 -C 20  alkyls (e.g., linear or branched C 1 -C 20  saturated alkyls), C 2 -C 20  alkenyls (e.g., linear or branched C 4 -C 20  dienyls, linear or branched C 6 -C 20  trienyls, and the like), and C 2 -C 20  alkynyls (e.g., linear or branched C 2 -C 20  alkynyls). C 1 -C 20  aliphatics can include C 3 -C 20  cyclic aliphatics (e.g., C 3 -C 20  cycloalkyls, C 4 -C 20  cycloalkenyls, or C 8 -C 20  cycloalkynyls). In certain embodiments, the aliphatic may comprise one or more cyclic aliphatic and/or one or more heteroatoms such as oxygen, nitrogen, or sulfur and may optionally be substituted with one or more substituents such as alkyl, halo, alkoxyl, hydroxy, amino, aryl, ether, ester or amide. An aliphatic group is unsubstituted or substituted with one or more substituent groups as described herein. For example, an aliphatic may be substituted with one or more (e.g., 1, 2, 3, 4, 5, or 6 independently selected substituents) of halogen, —COR′, —CO 2 H, —CO 2 R′, —CN, —OH, —OR′, —OCOR′, —OCO 2 R′, —NH 2 , —NHR′, —N(R′) 2 , —SR′ or —SO 2 R′, wherein each instance of R′ independently is C 1 -C 20  aliphatic (e.g., C 1 -C 20  alkyl, C 1 -C 15  alkyl, C 1 -C 10  alkyl, or C 1 -C 3  alkyl). In embodiments, R′ independently is an unsubstituted alkyl (e.g., unsubstituted C 1 -C 20  alkyl, C 1 -C 15  alkyl, C 1 -C 10  alkyl, or C 1 -C 3  alkyl). In embodiments, R′ independently is unsubstituted C 1 -C 3  alkyl. In embodiments, the aliphatic is unsubstituted. In embodiments, the aliphatic does not include any heteroatoms. 
     Alkyl: As used herein, the term “alkyl” means acyclic linear and branched hydrocarbon groups, e.g. “C 3 -C 30  alkyl” refers to alkyl groups having 1-30 carbons. An alkyl group may be linear or branched. Examples of alkyl groups include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, butyl, isobutyl, sec-butyl, tent-butyl, pentyl, isopentyl tert-pentylhexyl, isohexyl, etc. The term “lower alkyl” means an alkyl group straight chain or branched alkyl having 1 to 6 carbon atoms. Other alkyl groups will be readily apparent to those of skill in the art given the benefit of the present disclosure. An alkyl group may be unsubstituted or substituted with one or more substituent groups as described herein. For example, an alkyl group may be substituted with one or more (e.g., 1, 2, 3, 4, 5, or 6 independently selected substituents) of halogen, —COR′, —CO 2 H, —CO 2 R′, —CN, —OH, —OR′, —OCOR′, —OCO 2 R′, —NH 2 , —NHR′, —N(R′) 2 , —SR′ or —SO 2 R′, wherein each instance of R′ independently is C 1 -C 20  aliphatic (e.g., C 1 -C 20  alkyl, C 1 -C 15  alkyl, C 1 -C 10  alkyl, or C 1 -C 3  alkyl). In embodiments, R′ independently is an unsubstituted alkyl (e.g., unsubstituted C 1 -C 20  alkyl, C 1 -C 15  alkyl, C 1 -C 10  alkyl, or C 1 -C 3 alkyl). In embodiments, R′ independently is unsubstituted C 1 -C 3  alkyl. In embodiments, the alkyl is substituted (e.g., with 1, 2, 3, 4, 5, or 6 substituent groups as described herein). In embodiments, an alkyl group is substituted with a —OH group and may also be referred to herein as a “hydroxyalkyl” group, where the prefix denotes the —OH group and “alkyl” is as described herein. 
     Affixing the suffix “-ene” to a group indicates the group is a divalent moiety, e.g., arylene is the divalent moiety of aryl, and heteroarylene is the divalent moiety of heteroaryl. 
     Alkylene: The term “alkylene,” as used herein, represents a saturated divalent straight or branched chain hydrocarbon group and is exemplified by methylene, ethylene, isopropylene and the like. Likewise, the term “alkenylene” as used herein represents an unsaturated divalent straight or branched chain hydrocarbon group having one or more unsaturated carbon-carbon double bonds that may occur in any stable point along the chain, and the term “alkynylene” herein represents an unsaturated divalent straight or branched chain hydrocarbon group having one or more unsaturated carbon-carbon triple bonds that may occur in any stable point along the chain. In certain embodiments, an alkylene, alkenylene, or alkynylene group may comprise one or more cyclic aliphatic and/or one or more heteroatoms such as oxygen, nitrogen, or sulfur and may optionally be substituted with one or more substituents such as alkyl, halo, alkoxyl, hydroxy, amino, aryl, ether, ester or amide. For example, an alkylene, alkenylene, or alkynylene may be substituted with one or more (e.g., 1, 2, 3, 4, 5, or 6 independently selected substituents) of halogen, —COR′, —CO 2 H, —CO 2 R′, —CN, —OH, —OR′, —OCOR′, —OCO 2 R′, —N(R′) 2 , —SR′ or —SO 2 R′, wherein each instance of R′ independently is C 1 -C 20  aliphatic (e.g., C 1 -C 20  alkyl, C 1 -C 15  alkyl, C 1 -C 15  alkyl, or C 1 -C 3  alkyl). In embodiments, R′ independently is an unsubstituted alkyl (e.g., unsubstituted C 1 -C 20  alkyl, C 1 -C 15  alkyl, C 1 -C 10  alkyl, or C 1 -C 3  alkyl). In embodiments, R′ independently is unsubstituted C 1 -C 3  alkyl. In certain embodiments, an alkylene, alkenylene, or alkynylene is unsubstituted. In certain embodiments, an alkylene, alkenylene, or alkynylene does not include any heteroatoms. 
     Alkenyl: As used herein, “alkenyl” means any linear or branched hydrocarbon chains having one or more unsaturated carbon-carbon double bonds that may occur in any stable point along the chain, e.g. “C 2 -C 30  alkenyl” refers to an alkenyl group having 2-30 carbons. For example, an alkenyl group includes prop-2-enyl, but-2-enyl, but-3-enyl, 2-methylprop-2-enyl, hex-2-enyl, hex-5-enyl, 2,3-dimethylbut-2-enyl, and the like. In embodiments, the alkenyl comprises 1, 2, or 3 carbon-carbon double bond. In embodiments, the alkenyl comprises a single carbon-carbon double bond. In embodiments, multiple double bonds (e.g., 2 or 3) are conjugated. An alkenyl group may be unsubstituted or substituted with one or more substituent groups as described herein. For example, an alkenyl group may be substituted with one or more (e.g., 1, 2, 3, 4, 5, or 6 independently selected substituents) of halogen, —COR′, —CO 2 H, —CO 2 R′, —OH, —OR′, —OCOR′, —OCO 2 R′, —NH 2 , —NHR′, —N(R′) 2 , —SR′ or —SO 2 R′, wherein each instance of R′ independently is C 1 -C 20  aliphatic (e.g., C 1 -C 20  alkyl, C 1 -C 15  alkyl, C 1 -C 10  alkyl, or C 1 -C 3  alkyl). In embodiments, R′ independently is an unsubstituted alkyl (e.g., unsubstituted C 1 -C 20  alkyl, C 1 -C 15  alkyl, C 1 -C 10  alkyl, or C 1 -C 3  alkyl). In embodiments, R′ independently is unsubstituted C 1 -C 3  alkyl. In embodiments, the alkenyl is unsubstituted. In embodiments, the alkenyl is substituted (e.g., with 1, 2, 3, 4, 5, or 6 substituent groups as described herein). In embodiments, an alkenyl group is substituted with a —OH group and may also be referred to herein as a “hydroxyalkenyl” group, where the prefix denotes the —OH group and “alkenyl” is as described herein. 
     Alkynyl: As used herein, “alkynyl” means any hydrocarbon chain of either linear or branched configuration, having one or more carbon-carbon triple bonds occurring in any stable point along the chain, e.g. “C 2 -C 30  alkynyl” refers to an alkynyl group having 2-30 carbons. Examples of an alkynyl group include prop-2-ynyl, but-2-ynyl, but-3-ynyl, pent-2-ynyl, 3-methylpent-4-ynyl, hex-2-ynyl, hex-5-ynyl, etc. In embodiments, an alkynyl comprises one carbon-carbon triple bond. An alkynyl group may be unsubstituted or substituted with one or more substituent groups as described herein. For example, an alkynyl group may be substituted with one or more (e.g., 1, 2, 3, 4, 5, or 6 independently selected substituents) of halogen, —COR′, —CO 2 H, —CO 2 R′, —CN, —OH, —OR′, —OCOR′, —OCO 2 R′, —NH 2 , —NHR′, —N(R′) 2 , —SR′ or —SO 2 R′, wherein each instance of R′ independently is C 1 -C 20  aliphatic (e.g., C 1 -C 20  alkyl, C 1 -C 15  alkyl, C 1 -C 10  alkyl, or C 1 -C 3  alkyl). In embodiments, R′ independently is an unsubstituted alkyl (e.g., unsubstituted C 1 -C 20  alkyl, C 1 -C 15  alkyl, C 1 -C 10  alkyl, cr C 1 -C 3  alkyl). In embodiments, R′ independently is unsubstituted C 1 -C 3  alkyl. In embodiments, the alkynyl is unsubstituted. In embodiments, the alkynyl is substituted (e.g., with 1, 2, 3, 4, 5, or 6 substituent groups as described herein). 
     Aryl: The term “aryl” used alone or as part of a larger moiety as in “aralkyl,” refers to a monocyclic, bicyclic, or tricyclic carbocyclic ring system having a total of six to fourteen ring members, wherein said ring system has a single point of attachment to the rest of the molecule, at least one ring in the system is aromatic and wherein each ring in the system contains 4 to 7 ring members. In embodiments ;  an aryl group has 6 ring carbon atoms (“C 6  aryl,” e.g., phenyl). In some embodiments, an aryl group has 10 ring carbon atoms (“C 10  aryl,” e.g., naphthyl such as 1-naphthyl and 2-naphthyl). In some embodiments, an aryl group has 14 ring carbon atoms (“C 14  aryl,” e.g., anthracyl). “Aryl” also includes ring systems wherein the aryl ring, as defined above, is fused with one or more carbocyclyl or heterocyclyl groups wherein the radical or point of attachment is on the aryl ring, and in such instances, the number of carbon atoms continue to designate the number of carbon atoms in the aryl ring system. Exemplary aryls include phenyl, naphthyl, and anthracene. 
     Arylene: The term “arylene” as used herein refers to an aryl group that is divalent (that is, having two points of attachment to the molecule). Exemplary arylenes include phenylene (e.g., unsubstituted phenylene or substituted phenylene). 
     Halogen: As used herein, the term “halogen” means fluorine, chlorine, bromine, or iodine. 
     Heteroalkyl: The term “heteroalkyl” is meant a branched or unbranched alkyl, alkenyl, or alkynyl group having from 1 to 14 carbon atoms in addition to 1, 2, 3 or 4 heteroatoms independently selected from the group consisting of N, O, S, and P. Heteroalkyls include tertiary amines, secondary amines, ethers, thioethers, amides, thioamides, carbamates, thiocarbamates, hydrazones, imines, phosphodiesters, phosphoramidates, sulfonamides, and disulfides. A heteroalkyl group may optionally include monocyclic, bicyclic, or tricyclic rings, in which each ring desirably has three to six members. Examples of heteroalkyls include polyethers, such as methoxymethyl and ethoxyethyl. 
     Heteroalkylene: The term “heteroalkylene,” as used herein, represents a divalent form of a heteroalkyl group as described herein. 
     Heteroaryl: The term “heteroaryl,” as used herein, is fully unsaturated heteroatom-containing ring wherein at least one ring atom is a heteroatom such as, but not limited to, nitrogen and oxygen. 
     Heterocycloalkyl: The term “heterocycloalkyl,” as used herein, is a non-aromatic ring wherein at least one atom is a heteroatom such as, but not limited to, nitrogen, oxygen, sulfur, or phosphorus, and the remaining atoms are carbon. The heterocycloalkyl group can be substituted or unsubstituted. 
     Compounds of the Invention 
     Liposomal-based vehicles are considered an attractive carrier for therapeutic agents and remain subject to continued development efforts. While liposomal-based vehicles that comprise certain lipid components have shown promising results with regard to encapsulation, stability and site localization, there remains a great need for improvement of liposomal-based delivery systems. For example, a significant drawback of liposomal delivery systems relates to the construction of liposomes that have sufficient cell culture or in vivo stability to reach desired target cells and/or intracellular compartments, and the ability of such liposomal delivery systems to efficiently release their encapsulated materials to such target cells. 
     In particular, there remains a need for improved lipids compounds that demonstrate improved pharmacokinetic properties and which are capable of delivering macromolecules, such as nucleic acids to a wide variety cell types and tissues with enhanced efficiency. Importantly, there also remains a particular need for novel lipid compounds that are characterized as having reduced toxicity and are capable of efficiently delivering encapsulated nucleic acids and polynucleotides to targeted cells, tissues and organs. 
     Described herein a novel class of thioester cationic lipid compounds for improved in vivo delivery of therapeutic agents, such as nucleic acids. In particular, a thioester cationic lipid described herein may be used as a cationic lipid, optionally with other lipids, to formulate a lipid-based nanoparticle (e.g., liposome) for encapsulating therapeutic agents, such as nucleic acids (e.g., DNA, sIRNA, mRNA, microRNA) for therapeutic use. 
     In embodiments, compounds described herein can provide one or more desired characteristics or properties. That is, in certain embodiments, compounds described herein can be characterized as having one or more properties that afford such compounds advantages relative to other similarly classified lipids. For example, compounds disclosed herein can allow for the control and tailoring of the properties of liposomal compositions (e.g., lipid nanoparticles) of which they are a component. In particular, compounds disclosed herein can be characterized by enhanced transfection efficiencies and their ability to provoke specific biological outcomes. Such outcomes can include, for example enhanced cellular uptake, endosomal/lysosomal disruption capabilities and/or promoting the release of encapsulated materials (e.g., polynucleotides) intracellularly. Additionally, the compounds disclosed herein have advantageous pharmacokinetic properties, biodistribution, and efficiency (e.g., due to the different disassociate rates of the polymer group used). 
     Compounds of Formula (A) 
     Provided herein are compounds which are cationic lipids. For example, the cationic lipids of the present invention include compounds having a structure according to Formula (A), 
     
       
         
         
             
             
         
       
     
     or a pharmaceutically acceptable salt thereof, wherein 
     each R 1  is independently C 6 -C 30  aliphatic; 
     L 1  is independently —(CR 2a R 2b ) a —, —(CH 2 CH 2 S) b CH 2 CH 2 —, or —CH 2 CH 2 (OCH 2 CH 2 ) c —; 
     each R 2a  and R 2b  is independently hydrogen or C 1 -C 6  alkyl; 
     each n is independently an integer of 0-12; 
     each a is independently an integer of 1-12; 
     each b is independently an integer of 1-11; and 
     each c is independently an integer of 1-11. 
     In embodiments, each n is independently an integer of 0-12, 0-10, 0-6, 0-4, or 0-2. In embodiments, n is 1, 2, 3, or 4. In embodiments, each n is 0. In embodiments, each n is 1. In embodiments, each n is 2. In embodiments, each n is 3. In embodiments, each n is 4. In embodiments, each n is 5. In embodiments, each n is 6. In embodiments, each n is 7. In embodiments, each n is 8. In embodiments, each n is 9. In embodiments, each n is 10. In embodiments, each n is 11. In embodiments, each n is 12. 
     In embodiments, each R 2a  and R 2b  is independently hydrogen or methyl. 
     In embodiments, each L 1  is independently —(CH 2 ) a —, —(CHCH 3 ) a —, —(CH 2 CH 2 S) b CH 2 CH 2 —, or —CH 2 CH 2 (OCH 2 CH 2 ) c —. 
     In embodiments, L 1  is —(CH 2 ) a . In embodiments, each a is independently an integer of 1-10, 1-8, or 1-6. In embodiments, each a is independently 1, 2, 3, 4, 5, or 6. In embodiments, each a is independently 1. In embodiments, each a is independently 2. In embodiments, each a is independently 3. In embodiments, each a is independently 4. In embodiments, each a is independently 5. In embodiments, each a is independently 6. In embodiments, each a is independently 7. In embodiments, each a is independently 8. In embodiments, each a is independently 9. In embodiments, each a is independently 10. In embodiments, each a is independently 11. In embodiments, each a is independently 12. 
     In embodiments, a cationic lipid has the following structure: 
     
       
         
         
             
             
         
       
     
     or a pharmaceutically acceptable salt thereof. 
     In embodiments, a cationic lipid has the following structure: 
     
       
         
         
             
             
         
       
     
     or a pharmaceutically acceptable salt thereof. 
     In embodiments, a cationic lipid has the following structure: 
     
       
         
         
             
             
         
       
     
     or a pharmaceutically acceptable salt thereof. 
     In embodiments, L 1  is —(CHCH 3 ) a —. In embodiments, each a is independently an integer of 1-10, 1-8, or 1-6. In embodiments, each a is independently 1, 2, 3, 4, 5, or 6. In embodiments, each a is 1. In embodiments, each a is 2. In embodiments, each a is 3. In embodiments, each a is 4. In embodiments, each a is 5. In embodiments, each a is 6. In embodiments, each a is 7. In embodiments, each a is 8. In embodiments, each a is independently 9. In embodiments, each a is independently 10. In embodiments, each a is independently 11. In embodiments, each a is independently 12. 
     In embodiments, a cationic lipid has the following structure: 
     
       
         
         
             
             
         
       
     
     or a pharmaceutically acceptable salt thereof. 
     In embodiments, a cationic lipid has the following structure: 
     
       
         
         
             
             
         
       
     
     or a pharmaceutically acceptable salt thereof. 
     In embodiments, L 1  is —(CH 2 CH 2 S) b CH 2 CH 2 —. In embodiments, each a is independently an integer of 1-10, 1-8, or 1-6. In embodiments, b is 1, 2, 3, 4, or 5. In embodiments, each b is 1. In embodiments, each b is 2. In embodiments, each b is 3. In embodiments, each b is 4. In embodiments, each h is 5. In embodiments, each b is 6. In embodiments, each b is 7. In embodiments, each b is 8. In embodiments, each b is 9. In embodiments, each h is 10. In embodiments, each b is 11. 
     In embodiments, a cationic lipid has the following structure: 
     
       
         
         
             
             
         
       
     
     or a pharmaceutically acceptable salt thereof. 
     In embodiments, L 1  is —CH 2 CH 2 (OCH 2 CH 2 ) c —. In embodiments, c is an integer of 1-10, 1-8, or 1-6. In embodiments, c is 1, 2, 3, 4, or 5. In embodiments, c is 1. In embodiments, c is 2. In embodiments, c is 3. In embodiments, c is 4. In embodiments, c is 5. In embodiments, c is 6. In embodiments, c is 7. In embodiments, c is 8. In embodiments, c is 9. In embodiments, c is 10. In embodiments, c is 11. 
     
       
         
           
               
               
               
             
               
                 TABLE I 
               
               
                   
               
               
                 Compound 
                   
                 Acid + 
               
               
                 No. 
                 Chemical Structure 
                 Dithiol 
               
               
                   
               
             
            
               
                  1 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 A1 + B1 
               
               
                   
               
               
                  2 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 A1 + B2 
               
               
                   
               
               
                  3 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 A1 + B3 
               
               
                   
               
               
                  4 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 A1 + B4 
               
               
                   
               
               
                  5 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 A1 + B5 
               
               
                   
               
               
                  6 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 A1 + B6 
               
               
                   
               
               
                  7 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 A1 + B7 
               
               
                   
               
               
                  8 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 A2 + B1 
               
               
                   
               
               
                  9 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 A2 + B2 
               
               
                   
               
               
                 10 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 A2 + B3 
               
               
                   
               
               
                 11 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 A2 + B4 
               
               
                   
               
               
                 12 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 A2 + B5 
               
               
                   
               
               
                 13 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 A2 + B6 
               
               
                   
               
               
                 14 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 A2 + B7 
               
               
                   
               
               
                 15 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 A3 + B1 
               
               
                   
               
               
                 16 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 A3 + B2 
               
               
                   
               
               
                 17 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 A3 + B3 
               
               
                   
               
               
                 18 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 A3 + B4 
               
               
                   
               
               
                 19 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 A3 + B5 
               
               
                   
               
               
                 20 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 A3 + B6 
               
               
                   
               
               
                 21 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 A3 + B7 
               
               
                   
               
               
                 22 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 A4 + B1 
               
               
                   
               
               
                 23 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 A4 + B2 
               
               
                   
               
               
                 24 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 A4 + B3 
               
               
                   
               
               
                 25 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 A4 + B4 
               
               
                   
               
               
                 26 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 A4 + B5 
               
               
                   
               
               
                 27 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 A4 + B6 
               
               
                   
               
               
                 28 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 A4 + B7 
               
               
                   
               
               
                 29 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 A5 + B1 
               
               
                   
               
               
                 30 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 A5 + B2 
               
               
                   
               
               
                 31 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 A5 + B3 
               
               
                   
               
               
                 32 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 A5 + B4 
               
               
                   
               
               
                 33 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 A5 + B5 
               
               
                   
               
               
                 34 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 A5 + B6 
               
               
                   
               
               
                 35 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 A5 + B7 
               
               
                   
               
               
                 36 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 A6 + B1 
               
               
                   
               
               
                 37 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 A6 + B2 
               
               
                   
               
               
                 38 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 A6 + B3 
               
               
                   
               
               
                 39 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 A6 + B4 
               
               
                   
               
               
                 40 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 A6 + B5 
               
               
                   
               
               
                 41 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 A6 + B6 
               
               
                   
               
               
                 42 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 A6 + B7 
               
               
                   
               
               
                 43 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 A7 + B1 
               
               
                   
               
               
                 44 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 A7 + B2 
               
               
                   
               
               
                 45 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 A7 + B3 
               
               
                   
               
               
                 46 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 A7 + B4 
               
               
                   
               
               
                 47 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 A7 + B5 
               
               
                   
               
               
                 48 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 A7 + B6 
               
               
                   
               
               
                 49 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 A7 + B7 
               
               
                   
               
               
                 50 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 A8 + B1 
               
               
                   
               
               
                 51 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 A8 + B2 
               
               
                   
               
               
                 52 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 A8 + B3 
               
               
                   
               
               
                 53 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 A8 + B4 
               
               
                   
               
               
                 54 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 A8 + B5 
               
               
                   
               
               
                 55 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 A8 + B6 
               
               
                   
               
               
                 56 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 A8 + B7 
               
               
                   
               
               
                 57 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 A9 + B1 
               
               
                   
               
               
                 58 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 A9 + B2 
               
               
                   
               
               
                 59 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 A9 + B3 
               
               
                   
               
               
                 60 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 A9 + B4 
               
               
                   
               
               
                 61 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 A9 + B5 
               
               
                   
               
               
                 62 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 A9 + B6 
               
               
                   
               
               
                 63 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 A9 + B7 
               
               
                   
               
            
           
         
       
     
     In embodiments, a cationic lipid has the following structure: 
     
       
         
         
             
             
         
       
     
     or a pharmaceutically acceptable salt thereof. 
     In embodiments, each R 1  is C 6 -C 30  alkyl. In embodiments, each is unsubstituted C 6 -C 30  alkyl. In embodiments, each R 1  is substituted C 6 -C 30  alkyl. In embodiments, each R 1  is C 6 -C 24  alkyl. In embodiments, each is unsubstituted C 6 -C 24  alkyl. In embodiments, each R 1  is substituted C 6 -C 24  alkyl. In embodiments, an alkyl is a branched alkyl. In embodiments, an alkyl is a linear alkyl. In embodiments, each R 1  is C 8 H 17 , C 10 H 21 , or C 12 H 25 . 
     In embodiments, each R 1  is C 6 -C 30  alkenyl. In embodiments, each R 1  is unsubstituted C 6 -C 30  alkenyl. In embodiments, each R 1  is substituted C 6 -C 30  alkenyl. In embodiments, each R′ is C 6 -C 24  alkenyl. In embodiments, each R 1  is unsubstituted C 6 -C 24  alkenyl. In embodiments, each is substituted C 6 -C 24  alkenyl. In embodiments, an alkenyl is a branched alkenyl. In embodiments, an alkenyl is a linear alkenyl. In embodiments, an alkenyl is a mono-alkenyl. In embodiments, an alkenyl is a dienyl. In embodiments, an alkenyl is a trienyl. 
     In embodiments, each R 1  is C 6 -C 30  alkynyl. In embodiments, each R 1  is unsubstituted C 6 -C 30  alkynyl. In embodiments, each R 1  is substituted C 6 -C 30  alkynyl. In embodiments, each R 1  is C 6 -C 24  alkynyl. In embodiments, each R 1  is unsubstituted C 6 -C 24  alkynyl. In embodiments, each R 1  is substituted C 6 -C 24  alkynyl. In embodiments, an alkenyl is a branched alkynyl. In embodiments, an alkenyl is a linear alkynyl. 
     In embodiments, each is the same. 
     Exemplary Compounds 
     In embodiments, a cationic lipid is any one of Compounds 1-63. 
     In embodiments, a cationic lipid is Compound 1. In embodiments, a cationic lipid is Compound 2. In embodiments, a cationic lipid is Compound 3. In embodiments, a cationic lipid is Compound 4. In embodiments, a cationic lipid is Compound 5. In embodiments, a cationic lipid is Compound 6. In embodiments, a cationic lipid is Compound 7. In embodiments, a cationic lipid is Compound 8. In embodiments, a cationic lipid is Compound 9. In embodiments, a cationic lipid is Compound 10. In embodiments, a cationic lipid is Compound 11. In embodiments, a cationic lipid is Compound 12. In embodiments, a cationic lipid is Compound 13. In embodiments, a cationic lipid is Compound 14. In embodiments, a cationic lipid is Compound 15. In embodiments, a cationic lipid is Compound 16. In embodiments, a cationic lipid is Compound 17. In embodiments, a cationic lipid is Compound 18. In embodiments, a cationic lipid is Compound 19. In embodiments, a cationic lipid is Compound 20. In embodiments, a cationic lipid is Compound 21. In embodiments, a cationic lipid is Compound 22. In embodiments, a cationic lipid is Compound 23. In embodiments, a cationic lipid is Compound 24. In embodiments, a cationic lipid is Compound 25. In embodiments, a cationic lipid is Compound 26. In embodiments, a cationic lipid is Compound 27. In embodiments, a cationic lipid is Compound 28. In embodiments, a cationic lipid is Compound 29. In embodiments, a cationic lipid is Compound 30. In embodiments, a cationic lipid is Compound 31. In embodiments, a cationic lipid is Compound 32. In embodiments, a cationic lipid is Compound 33. In embodiments, a cationic lipid is Compound 34. In embodiments, a cationic lipid is Compound 35. In embodiments, a cationic lipid is Compound 36. In embodiments, a cationic lipid is Compound 37. In embodiments, a cationic lipid is Compound 38. In embodiments, a cationic lipid is Compound 39. In embodiments, a cationic lipid is Compound 40. In embodiments, a cationic lipid is Compound 41. In embodiments, a cationic lipid is Compound 42. In embodiments, a cationic lipid is Compound 43. In embodiments, a cationic lipid is Compound 44. In embodiments, a cationic lipid is Compound 45. In embodiments, a cationic lipid is Compound 46. In embodiments, a cationic lipid is Compound 47. In embodiments, a cationic lipid is Compound 48. In embodiments, a cationic lipid is Compound 49. In embodiments, a cationic lipid is Compound 50. In embodiments, a cationic lipid is Compound 51. In embodiments, a cationic lipid is Compound 52. In embodiments, a cationic lipid is Compound 53. In embodiments, a cationic lipid is Compound 54. In embodiments, a cationic lipid is Compound 55. In embodiments, a cationic lipid is Compound 56. In embodiments, a cationic lipid is Compound 57. In embodiments, a cationic lipid is Compound 58. In embodiments, a cationic lipid is Compound 59. In embodiments, a cationic lipid is Compound 60. In embodiments, a cationic lipid is Compound 61. In embodiments, a cationic lipid is Compound 62. In embodiments, a cationic lipid is Compound 63. 
     Synthesis of Compounds of the Invention 
     The compounds described herein (e.g., a compound of Formula (A), such as any of Formulae (I)-(VII) or any one of Compounds 1-63) can he prepared according to methods known in the art, including the exemplary syntheses of the Examples provided herein. 
     Nucleic Acids 
     The compounds described herein (e.g., a compound of Formula (A), such as any of Formulae (I)-(VII) or any one of Compounds 1-63) can be used to prepare compositions useful for the delivery of nucleic acids. 
     Synthesis of Nucleic Acids 
     Nucleic acids according to the present invention may be synthesized according to any known methods. For example, mRNAs according to the present invention may be synthesized via in vitro transcription (IVT). Briefly, IVT is typically performed with a linear or circular DNA template containing a promoter, a pool of ribonucleotide triphosphates, a buffer system that may include DTT and magnesium ions, and an appropriate RNA polymerase (e.g., T3, T7, mutated T7 or SP6 RNA polymerase), DNAse I, pyrophosphatase, and/or RNAse inhibitor. The exact conditions will vary according to the specific application. 
     In some embodiments, for the preparation of mRNA according to the invention, a DNA template is transcribed in vitro. A suitable DNA template typically has a promoter, for example a T3, T7, mutated T7 or SP6 promoter, for in vitro transcription, followed by desired nucleotide sequence for desired mRNA and a termination signal. 
     Desired mRNA sequence(s) according to the invention may be determined and incorporated into a DNA template using standard methods. For example, starting from a desired amino acid sequence (e.g., an enzyme sequence), a virtual reverse translation is carried out based on the degenerated genetic code. Optimization algorithms may then be used for selection of suitable codons. Typically, the G/C content can be optimized to achieve the highest possible G/C content on one hand, taking into the best possible account the frequency of the tRNAs according to codon usage on the other hand. The optimized RNA sequence can be established and displayed, for example, with the aid of an appropriate display device and compared with the original (wild-type) sequence. A secondary structure can also be analyzed to calculate stabilizing and destabilizing properties or, respectively, regions of the RNA. 
     As described above, the term “nucleic acid,” in its broadest sense, refers to any compound and/or substance that is or can be incorporated into a polynucleotide chain. DNA may be in the form of antisense DNA, plasmid DNA, parts of a plasmid DNA, pre-condensed DNA, a product of a polymerase chain reaction (PCR), vectors (e.g., P1, PAC, BAC, YAC, artificial chromosomes), expression cassettes, chimeric sequences, chromosomal DNA, or derivatives of these groups. RNA may be in the form of messenger RNA (mRNA), ribosomal RNA (rRNA), signal recognition particle RNA (7 SL RNA or SRP RNA), transfer RNA (tRNA), transfer-messenger RNA (tmRNA), small nuclear RNA (snRNA), small nucleolar RNA (snoRNA), SmY RNA, small Cajal body-specific RNA (scaRNA), guide RNA (gRNA), ribonuclease P (RNase P), Y RNA, telomerase RNA component (TERC), spliced leader RNA (SL RNA), antisense RNA (aRNA or asRNA), cis-natural antisense transcript (cis-NAT), CRISPR RNA (crRNA), long noncoding RNA (lncRNA), microRNA (miRNA), piwi-interacting RNA (piRNA), small interfering RNA (siRNA), transacting siRNA (tasiRNA), repeat associated siRNA (rasiRNA), 73K RNA, retrotransposons, a viral genome, a viroid, satellite RNA, or derivatives of these groups. In some embodiments, a nucleic acid is a mRNA encoding a protein. 
     Synthesis of mRNA 
     mRNAs according to the present invention may be synthesized according to any of a variety of known methods. For example, mRNAs according to the present invention may be synthesized via in vitro transcription (IVT). Briefly, IVT is typically performed with a linear or circular DNA template containing a promoter, a pool of ribonucleotide triphosphates, a buffer system that may include DTT and magnesium ions, and an appropriate RNA polymerase (e.g., T3, T7 or S?6 RNA polymerase), DNAse I, pyrophosphatase, and/or RNAse inhibitor. The exact conditions will vary according to the specific application. The presence of these reagents is undesirable in the final product according to several embodiments and may thus be referred to as impurities and a preparation containing one or more of these impurities may be referred to as an impure preparation. In some embodiments, the in vitro transcribing occurs in a single batch. 
     In some embodiments, for the preparation of mRNA according to the invention, a DNA template is transcribed in vitro. A suitable DNA template typically has a promoter, for example a T3, T7 or SP6 promoter, for in vitro transcription, followed by desired nucleotide sequence for desired mRNA and a termination signal. 
     Desired mRNA sequence(s) according to the invention may be determined and incorporated into a DNA template using standard methods. For example, starting from a desired amino acid sequence (e.g., an enzyme sequence), a virtual reverse translation is carried out based on the degenerated genetic code. Optimization algorithms may then be used for selection of suitable codons. Typically, the G/C content can be optimized to achieve the highest possible G/C content on one hand, taking nto the best possible account the frequency of the tRNAs according to codon usage on the other hand. The optimized RNA sequence can be established and displayed, for example, with the aid of an appropriate display device and compared with the original (wild-type) sequence. A secondary structure can also be analyzed to calculate stabilizing and destabilizing properties or, respectively, regions of the RNA. 
     Modified mRNA 
     in some embodiments, mRNA according to the present invention may be synthesized as unmodified or modified mRNA. Modified mRNA comprise nucleotide modifications in the RNA. A modified mRNA according to the invention can thus include nucleotide modification that are, for example, backbone modifications, sugar modifications or base modifications. In some embodiments, mRNAs may be synthesized from naturally occurring nucleotides and/or nucleotide analogues (modified nucleotides) including, but not limited to, purines (adenine (A), guanine (G)) or pyrimidines (thymine (T), cytosine (C), uracil (U)), and as modified nucleotides analogues or derivatives of purines and pyrimidines, such as e.g., 1-methyl-adenine, 2-methyl-adenine, 2-methylthio-N-6-isopentenyl-adenine, N6-methyl-adenine, N6-iscpentenyl-adenine, 2-thio-cytosine, 3-methyl-cytosine, 4-acetyl-cytosine, 5-methyl-cytosine, 2,6-diaminopurine, 1-methyl-guanine, 2-methyl-guanine, 2,2-dimethyl-guanine, 7-methyl-guanine, inosine, 1-methyl-inosine, pseudouracil (5-uracil), dihydro-uracil, 2-thio-uracil, 4-thio-uracil, 5-carboxymethylaminomethyl-2-thio-uracil, 5-(carboxyhydroxymethyl)-uracil, 5-fluoro-uracil, 5-bromo-uracil, 5-carboxymethylaminomethyl-uracil, 5-methyl-2-thio-uracil, 5-methyl-uracil, N-uracil-5-oxyacetic acid methyl ester, 5-methylaminomethyl-uracil, 5-methoxyaminomethyl-2-thio-uracil, 5′-methoxycarbonylmethyl-uracil, 5-methoxy-uracil, uracil-5-oxyacetic acid methyl ester, uracil-5-oxyacetic acid (v), 1-methyl-pseudouracil, queuosine, beta-D-mannosyl-queuosine, wybutoxosine, and phosphoramidates, phosphorothioates, peptide nucleotides, methylphosphonates, 7-deazaguanosine, 5-methylcytosine and inosine. The preparation of such analogues is known to a person skilled in the art e.g., from the U.S. Pat. Nos. 4,373,071, 4,401,796, 4,415,732, 4,458,066, 4,500,707, 4,668,777, 4,973,679, 5,047,524, 5,132,418, 5,153,319, 5,262,530 and 5,700,642, the disclosures of which are incorporated by reference in their entirety. 
     In some embodiments, mRNAs may contain RNA backbone modifications. Typically, a backbone modification is a modification in which the phosphates of the backbone of the nucleotides contained in the RNA are modified chemically. Exemplary backbone modifications typically include, but are not limited to, modifications from the group consisting of methylphosphonates, methylphosphoramidates, phosphoramidates, phosphorothioates (e.g., cytidine 5′-O-(1-thiophosphate)), boranophosphates, positively charged guanidinium groups etc., which means by replacing the phosphodiester linkage by other anionic, cationic or neutral groups. 
     In some embodiments, mRNAs may contain sugar modifications. A typical sugar modification is a chemical modification of the sugar of the nucleotides it contains including, but not limited to, sugar modifications chosen from the group consisting of 4′-thio-ribonucleotide (see, e.g., US Patent Application Publication No. US 2016/0031928, incorporated by reference herein), 2′-deoxy-2′-fluoro-oligoribonucleotide (2′-fluoro-2′-deoxycytidine 5′-triphosphate, 2′-fluoro-2′-deoxyuridine 5′-triphosphate), 2′-deoxy-2′-deamine-oligoribonucleotide (2′-amino-2′-deoxycytidine 5′-triphosphate, 2′-amino-2′-deoxyuridine 5′-triphosphate), 2′-O-alkyloligoribonucleotide, 2′-deoxy-2′-C-alkyloligoribonucleotide (2′-O-methylcytidine triphosphate, 2′-methyluridine 5′-triphosphate), 2′-O-alkyloligoribonucleotide, and isomers thereof (2′-aracytidine 5′-triphosphate, 2′-arauridine 5′-triphosphate), or azidotriphosphates (2′-azido-2′-deoxycytidine 5′-triphosphate, 2′-azido-2′-deoxyuridine 5′-triphosphate). 
     In some embodiments, mRNAs may contain modifications of the bases of the nucleotides (base modifications). A modified nucleotide which contains a base modification is also called a base-modified nucleotide. Examples of such base-modified nucleotides include, but are not limited to, 2-amino-6-chloropurine riboside 5′-triphosphate, 2-aminoadenosine 5′-triphosphate, 2-thiocytidine 5′-triphosphate, 2-thiouridine 5′-triphosphate, 4-thiouridine 5′-triphosphate, 5-aminoallylcytidine 5′-triphosphate, 5-aminoallyluridine 5′-triphosphate, 5-bromocytidine 5′-triphosphate, 5-bromouridine 5′-triphosphate, 5-iodocytidine 5′-triphosphate, 5-iodouridine 5′-triphosphate, 5-methylcytidine 5′-triphosphate, 5-methyluridine 5′-triphosphate, 6-azacytidine 5′-triphosphate, 6-azauridine 5-triphosphate, 6-chloropurine riboside 5′-triphosphate, 7-deazaadenosine 5′-triphosphate, 7-deazaguanosine 5′-triphosphate, 8-azaadenosine 5′-triphosphate, 8-azidoadenosine 5′-triphosphate, benzimidazole riboside 5′-triphosphate, N1-methyladenosine 5′-triphosphate, N1-methylguanosine 5′-triphosphate, N6-methyladenosine triphosphate, O6-methylguanosine 5′-triphosphate, pseudouridine 5′-triphosphate, puromycin 5′-triphosphate or xanthosine 5′-triphosphate. 
     Typically, mRNA synthesis includes the addition of a “cap” on the N-terminal (5′) end, and a “tail” on the C-terminal (3′) end. The presence of the cap is important in providing resistance to nucleases found in most eukaryotic cells. The presence of a “tail” serves to protect the mRNA from exonuclease degradation. 
     Thus, in some embodiments, mRNAs include a 5′ cap structure. A 5′ cap is typically added as follows: first, an RNA terminal phosphatase removes one of the terminal phosphate groups from the 5′ nucleotide, leaving two terminal phosphates; guanosine triphosphate (GTP) is then added to the terminal phosphates via a guanylyl transferase, producing a 5′5′5 triphosphate linkage; and the 7-nitrogen of guanine is then methylated by a methyltransferase. Examples of cap structures include, but are not limited to, m7G(5′)ppp (5′(A,G(5′)ppp(5′)A and G(5′)ppp(5′)G. 
     In some embodiments, mRNAs include a 3′ poly(A) tail structure. A poly-A tail on the 3′ terminus of mRNA typically includes about 10 to 300 adenosine nucleotides (e.g., about 10 to 200 adenosine nucleotides, about 10 to 150 adenosine nucleotides, about 10 to 100 adenosine nucleotides, about 20 to 70 adenosine nucleotides, or about 20 to 60 adenosine nucleotides). In some embodiments, mRNAs include a 3′ poly(C) tail structure. A suitable poly-C tail on the 3′ terminus of mRNA typically include about 10 to 200 cytosine nucleotides (e.g., about 10 to 150 cytosine nucleotides, about 10 to 100 cytosine nucleotides, about 20 to 70 cytosine nucleotides, about 20 to 60 cytosine nucleotides, or about 10 to 40 cytosine nucleotides). The poly-C tail may be added to the poly-A tail or may substitute the poly-A tail. 
     In some embodiments, mRNAs include a 5′ and/or 3′ untranslated region. In some embodiments, a 5′ untranslated region includes one or more elements that affect an mRNA&#39;s stability or translation, for example, an iron responsive element. In some embodiments, a 5′ untranslated region may be between about 50 and 500 nucleotides in length. 
     in some embodiments, a 3′ untranslated region includes one or more of a polyadenylation signal, a binding site for proteins that affect an mRNA&#39;s stability of location in a cell, or one or more binding sites for miRNAs. In some embodiments, a 3′ untranslated region may be between 50 and 500 nucleotides in length or longer. 
     Cap Structure 
     In some embodiments, in some embodiments, mRNAs (e.g., mRNAs encoding CFTR) include a 5′ cap structure. A 5′ cap is typically added as follows: first, an RNA terminal phosphatase removes one of the terminal phosphate groups from the 5′ nucleotide, leaving two terminal phosphates; guanosine triphosphate (GTP) is then added to the terminal phosphates via a guanylyl transferase, producing a 5′-5′ triphosphate linkage; and the 7-nitrogen of guanine is then methylated by a methyltransferase. In some embodiments, the nucleotide forming the cap is further methylated at the 3′position. In some embodiments, the nucleotide directly adjacent to the cap is further methylated at the 2′ position. Examples of cap structures include, but are not limited to, m7G(5′)ppp(5′)(2′OMeG), m7G(5′)ppp(5′)(2′OMeA), m7(3′OMeG)(5′)ppp(5′)(2′OMeG), m7(3′OMeG)(5′)ppp(5′)(2′OMeA), m7G(5′)ppp (5′(A,G(5′)ppp(5′)A and G(5′)ppp(5′)G. In a specific embodiment, the cap structure is m7G(5′)ppp(5′)(2′OMeG). 
     Naturally occurring cap structures comprise a 7-methyl guanosine that is linked via a triphosphate bridge to the 5′-end of the first transcribed nucleotide, resulting in a dinucleotide cap of m 7 G(5′)ppp(5′)N, where N is any nucleoside. In vivo, the cap is added enzymatically. The cap is added in the nucleus and is catalyzed by the enzyme guanylyl transferase. The addition of the cap to the 5′ terminal end of RNA occurs immediately after initiation of transcription. The terminal nucleoside is typically a guanosine, and is in the reverse orientation to all the other nucleotides, i.e., G(5′)ppp(5′)GpNpNp. 
     In some embodiments, the cap for mRNA produced by in vitro transcription is m 7 G(5′)ppp(5′)G, which has been used as the dinucleotide cap in transcription with T7 or SP6 RNA polymerase in vitro to obtain RNAs having a cap structure in their 5′-termini. The prevailing method for the in vitro synthesis of capped mRNA employs a pre-formed dinucleotide of the form m 7 G(5′)ppp(5′)G (“m 7 GpppG”) as an initiator of transcription. 
     In some embodiments, a form of a synthetic dinucleotide cap used in in vitro translation experiments is the Anti-Reverse Cap Analog (“ARCA”) or modified ARCA, which is generally a modified cap analog in which the 2′ or 3′ OH group is replaced with —OCH 3 . 
     Additional cap analogs include, but are not limited to, a chemical structures selected from the group consisting of m 7 GpppG, m 7 GpppA, m 7 GpppC; unmethylated cap analogs (e.g., GpppG); dimethylated cap analog (e.g., m 2,7 GpppG), trimethylated cap analog (e.g., m 2,2,7 GpppG), dimethylated symmetrical cap analogs (e.g., m 7 Gpppm 7 G), or anti reverse cap analogs (e.g., ARCA; m 7 , 2′Ome GpppG, m 72′d GpppG, m 7,3′Ome GpppG, m 7,3′d GpppG and their tetraphosphate derivatives) (see, e.g., Jemielity, J. et al. , “ Novel ‘anti - reverse’ cap analogs with superior translational properties ”, RNA, 9: 1108-1122 (2003)). 
     In some embodiments, a suitable cap is a 7-methyl guanylate (“m 7 G”) linked via a triphosphate bridge to the 5′-end of the first transcribed nucleotide, resulting in m 7 G(5′)ppp(5′)N, where N is any nucleoside. A preferred embodiment of a m 7 G cap utilized in embodiments of the invention is m 7 G(5′)ppp(5′)G. 
     In some embodiments, the cap is a Cap0 structure. Cap0 structures lack a 2′-O-methyl residue of the ribose attached to bases 1 and 2. In some embodiments, the cap is a Cap1 structure. Cap1 structures have a 2′-O-methyl residue at base 2. In some embodiments, the cap is a Cap2 structure. Cap2 structures have a 2′-O-methyl residue attached to both bases 2 and 3. 
     A variety of m 7 G cap analogs are known in the art, many of which are commercially available. These include the m 7 GpppG described above, as well as the ARCA 3′-OCH 3  and 2′-OCH 3 cap analogs (Jemielity, J. et al., RNA, 9: 1108-1122 (2003)). Additional cap analogs for use in embodiments &amp;the invention include N7-benzylated dinucleoside tetraphosphate analogs (described in Grudzien, E. et al. , RNA, 10: 1479-1487 (2004)), phosphorothioate cap analogs (described in Grudzien-Nogalska, E., et al., RNA, 13: 1745-1755 (2007)), and cap analogs (including biotinylated cap analogs) described in U.S. Pat. Nos. 8,093,367 and 8,304,529, incorporated by reference herein. 
     Additional cap structures are also described in published US Application No. US 2016/0032356 and U.S. Provisional Application 62/464,327, filed Feb. 27, 2017, which are incorporated herein by reference. 
     Tail Structure 
     Typically, the presence of a “tail” serves to protect the mRNA from exonuclease degradation. The poly A tail is thought to stabilize natural messengers and synthetic sense RNA. Therefore, in certain embodiments a long poly A tail can be added to an mRNA molecule thus rendering the RNA more stable. Poly A tails can be added using a variety of art-recognized techniques. For example, long poly A tails can be added to synthetic or in vitro transcribed RNA using poly A polymerase (Yokoe, etal. Nature Biotechnology, 1996; 14: 1252-1256). A transcription vector can also encode long poly A tails. In addition, poly A tails can be added by transcription directly from PCR products. Poly A may also be ligated to the 3′ end of a sense RNA with RNA ligase (see, e.g., Molecular Cloning A Laboratory Manual, 2nd Ed., ed. by Sambrook, Fritsch and Maniatis (Cold Spring Harbor Laboratory Press: 1991 edition)). 
     In some embodiments, mRNAs include a 3′ poly(A) tail structure, Typically, the length of the poly A tail can be at least about 10, 50, 100, 200, 300, 400 at least 500 nucleotides. In some embodiments, a poly-A tail on the 3′ terminus of mRNA typically includes about 10 to 300 adenosine nucleotides (e.g., about 10 to 200 adenosine nucleotides, about 10 to 150 adenosine nucleotides, about 10 to 100 adenosine nucleotides, about 20 to 70 adenosine nucleotides, or about 20 to 60 adenosine nucleotides). In some embodiments, mRNAs include a 3′ poly(C) tail structure. A suitable poly-C tail on the 3′ terminus of mRNA typically include about 10 to 200 cytosine nucleotides (e.g., about 10 to 150 cytosine nucleotides, about 10 to 100 cytosine nucleotides, about 20 to 70 cytosine nucleotides, about 20 to 60 cytosine nucleotides, or about 10 to 40 cytosine nucleotides). The poly-C tail may be added to the poly-A tail or may substitute the poly-A tail. 
     in some embodiments, the length of the poly A or poly C tail is adjusted to control the stability of a modified sense mRNA molecule of the invention and, thus, the transcription of protein. For example, since the length of the poly A tail can influence the half-life of a sense mRNA molecule, the length of the poly A tail can be adjusted to modify the level of resistance of the mRNA to nucleases and thereby control the time course of polynucleotide expression and/or polypeptide production in a target cell. 
     5′ and 3′ Untranslated Region 
     In some embodiments, mRNAs include a 5′ and/or 3′ untranslated region. In some embodiments, a 5′ untranslated region includes one or more elements that affect an mRNA&#39;s stability or translation, for example, an iron responsive element. In some embodiments, a 5′ untranslated region may be between about 50 and 500 nucleotides in length. 
     In some embodiments, a 3′ untranslated region includes one or more of a polyadenylation signal, a binding site for proteins that affect an mRNA&#39;s stability of location in a cell, or one or more binding sites for miRNAs. In some embodiments, a 3′ untranslated region may be between 50 and 500 nucleotides in length or longer. 
     Exemplary 3′ and/or 5′ UTR sequences can be derived from mRNA molecules which are stable (e.g., globin, actin, GAPDH, tubulin, histone, or citric acid cycle enzymes) to increase the stability of the sense mRNA molecule. For example, a 5′ UTR sequence may include a partial sequence of a CMV immediate-early 1 (IE1) gene, or a fragment thereof to improve the nuclease resistance and/or improve the half-life of the polynucleotide. Also contemplated is the inclusion of a sequence encoding human growth hormone (hGH), or a fragment thereof to the 3′ end or untranslated region of the polynucleotide (e.g., mRNA) to further stabilize the polynucleotide. Generally, these modifications improve the stability and/or pharmacokinetic properties (e.g., half-life) of the polynucleotide relative to their unmodified counterparts, and include, for example modifications made to improve such polynucleotides&#39; resistance to in vivo nuclease digestion. 
     Pharmaceutical Formulations of Cationic Lipids and Nucleic Acids 
     In certain embodiments, the compounds described herein (e.g., a compound of Formula (A), such as any of Formulae (I)-(VII) or any one of Compounds 1-63), as well as pharmaceutical and liposomal compositions comprising such lipids, can be used in formulations to facilitate the delivery of encapsulated materials (e.g., one or more polynucleotides such as mRNA) to, and subsequent transfection of one or more target cells. For example, in certain embodiments cationic lipids described herein and compositions such as liposomal compositions comprising such lipids) are characterized as resulting in one or more of receptor-mediated endocytosis, clathrin-mediated and caveolae-mediated endocytosis, phagocytosis and macropinocytosis, fusogenicity, endosomal or lysosomal disruption and/or releasable properties that afford such compounds advantages relative other similarly classified lipids. 
     According to the present invention, a nucleic acid, e.g., mRNA encoding a protein (e.g., a full length, fragment or portion of a protein) as described herein may be delivered via a delivery vehicle comprising a compound as described herein (e.g., a compound of Formula (A), such as any of Formulae (I)-(VII) or any one of Compounds 1-63). 
     As used herein, the terms “delivery vehicle,” “transfer vehicle,” “nanoparticle,” or grammatical equivalents thereof, are used interchangeably. 
     For example, the present invention provides a composition (e.g., a pharmaceutical composition) comprising a compound described herein (e.g., a compound of Formula (A), such as any of Formulae (I)-(VII) or any one of Compounds 1-63) and one or more polynucleotides. A composition (e.g., a pharmaceutical composition) may further comprise one or more cationic lipids, one or more non-cationic lipids, one or more cholesterol-based lipids and/or one or more PEG-modified lipids. 
     In certain embodiments a composition exhibits an enhanced (e.g., increased) ability to transfect one or more target cells. Accordingly, also provided herein are methods of transfecting one or more target cells. Such methods generally comprise the step of contacting the one or more target cells with the cationic lipids and/or pharmaceutical compositions disclosed herein (e.g., a liposomal formulation comprising a compound described herein (e.g., a compound of Formula (A), such as any of Formulae (I)-(VII) or any one of Compounds 1-63) encapsulating one or more polynucleotides) such that the one or more target cells are transfected with the materials encapsulated therein (e.g., one or more polynucleotides). As used herein, the terms “transfect” or “transfection” refer to the intracellular introduction of one or more encapsulated materials (e.g., nucleic acids and/or polynucleotides) into a cell, or preferably into a target cell. The introduced polynucleotide may be stably or transiently maintained in the target cell. The term “transfection efficiency” refers to the relative amount of such encapsulated material (e.g., polynucleotides) up-taken by, introduced into, and/or expressed by the target cell which is subject to transfection. In practice, transfection efficiency may be estimated by the amount of a reporter polynucleotide product produced by the target cells following transfection. In certain embodiments, the compounds and pharmaceutical compositions described herein demonstrate high transfection efficiencies thereby improving the likelihood that appropriate dosages of the encapsulated materials (e.g., one or more polynucleotides) will be delivered to the site of pathology and subsequently expressed, while at the same time minimizing potential systemic adverse effects or toxicity associated with the compound or their encapsulated contents. 
     Following transfection of one or more target cells by, for example, the polynucleotides encapsulated in the one or more lipid nanoparticles comprising the pharmaceutical or liposomal compositions disclosed herein, the production of the product (e.g., a polypeptide or protein) encoded by such polynucleotide may be preferably stimulated and the capability of such target cells to express the polynuclectide and produce, for example, a polypeptide or protein of interest is enhanced. For example, transfection of a target cell by one or more compounds or pharmaceutical compositions encapsulating mRNA will enhance (i.e., increase) the production of the protein or enzyme encoded by such mRNA. 
     Further, delivery vehicles described herein (e.g., liposomal delivery vehicles) may be prepared to preferentially distribute to other target tissues, cells or organs, such as the heart, lungs, kidneys, spleen. In embodiments, the lipid nanoparticles of the present invention may be prepared to achieve enhanced delivery to the target cells and tissues. For example, polynucleotides (e.g., mRNA) encapsulated in one or more of the compounds or pharmaceutical and liposomal compositions described herein can be delivered to and/or transfect targeted cells or tissues. In some embodiments, the encapsulated polynucleotides (e.g., mRNA) are capable of being expressed and functional polypeptide products produced (and in some instances excreted) by the target cell, thereby conferring a beneficial property to, for example the target cells or tissues. Such encapsulated polynucleotides (e.g., mRNA) may encode, for example, a hormone, enzyme, receptor, polypeptide, peptide or other protein of interest. 
     Liposomal Delivery Vehicles 
     In some embodiments, a composition is a suitable delivery vehicle. In embodiments, a composition is a liposomal delivery vehicle, e.g., a lipid nanoparticle. 
     The terms “liposomal delivery vehicle” and “liposomal composition” are used interchangeably. 
     Enriching liposomal compositions with one or more of the cationic lipids disclosed herein may be used as a means of improving (e.g., reducing) the toxicity or otherwise conferring one or more desired properties to such enriched liposomal composition (e.g., improved delivery of the encapsulated polynucleotides to one or more target cells and/or reduced in vivo toxicity of a liposomal composition). Accordingly, also contemplated are pharmaceutical compositions, and in particular liposomal compositions, that comprise one or more of the cationic lipids disclosed herein. 
     Thus, in certain embodiments, the compounds described herein (e.g., a compound of Formula (A), such as any of Formulae (I)-(VII) or any one of Compounds 1-63) may be used as a component of a liposomal composition to facilitate or enhance the delivery and release of encapsulated materials (e.g., one or more therapeutic agents) to one or more target cells (e.g., by permeating or fusing with the lipid membranes of such target cells). 
     As used herein, liposomal delivery vehicles, e.g., lipid nanoparticles, are usually characterized as microscopic vesicles having an interior aqua space sequestered from an outer medium by a membrane of one or more bilayers. Bilayer membranes of liposomes are typically formed by amphiphilic molecules, such as lipids of synthetic or natural origin that comprise spatially separated hydrophilic and hydrophobic domains (Lasic, Trends Biotechnol., 16: 307-321, 1998). Bilayer membranes of the liposomes can also be formed by amphophilic polymers and surfactants (e.g., polymerosomes, niosomes, etc.). In the context of the present invention, a liposomal delivery vehicle typically serves to transport a desired mRNA to a target cell or tissue. 
     In certain embodiments, such compositions (e.g., liposomal compositions) are loaded with or otherwise encapsulate materials, such as for example, one or more biologically-active polynucleotides (e.g., mRNA). 
     In embodiments, a composition (e.g., a pharmaceutical composition) comprises an mRNA encoding a protein, encapsulated within a liposome. In embodiments, a liposome comprises one or more cationic lipids, one or more non-cationic lipids, one or more cholesterol-based lipids and one or more PEG-modified lipids, and wherein at least one PEG-modified lipid is a compound as described herein (e.g., a compound of Formula (A), such as any of Formulae (I)-(VII) or any one of Compounds 1-63). In embodiments, a composition comprises an mRNA encoding for a protein (e.g., any protein described herein). In embodiments, a composition comprises an mRNA encoding for cystic fibrosis transmembrane conductance regulator (CFTR) protein. In embodiments, a composition comprises an mRNA encoding for ornithine transcarbamylase (OTC) protein. 
     In embodiments, a composition a pharmaceutical composition) comprises a nucleic acid encapsulated within a liposome, wherein the liposome comprises any compound described herein (e,g., a compound of Formula (A), such as any of Formulae (I)-(VII) or any one of Compounds 1-63) as described herein. 
     In embodiments, a nucleic acid is an mRNA encoding a peptide or protein. In embodiments, an mRNA encodes a peptide or protein for use in the delivery to or treatment of the lung of a subject or a lung cell (e.g., an mRNA encodes cystic fibrosis transmembrane conductance regulator (CFTR) protein). In embodiments, an mRNA encodes a peptide or protein for use in the delivery to or treatment of the liver of a subject or a liver cell (e.g., an mRNA encodes ornithine transcarbamylase (OTC) protein). Still other exemplary mRNAs are described herein. 
     In embodiments, a liposomal delivery vehicle (e.g., a lipid nanoparticle) can have a net positive charge. 
     In embodiments, a liposomal delivery vehicle (e.g., a lipid nanoparticle) can have a net negative charge. 
     In embodiments, a liposomal delivery vehicle (e.g., a lipid nanoparticle) can have a net neutral charge. 
     In embodiments, a lipid nanoparticle that encapsulates a nucleic acid (e.g., mRNA encoding a peptide or protein) comprises one or more compounds described herein ((e.g., a compound of Formula (A), such as any of Formulae (I)-(VII) or any one of Compounds 1-63). 
     For example, the amount of a compound as described herein (e.g., a compound of Formula (A), such as any of Formulae (I)-(VII) or any one of Compounds 1-63) in a composition can be described as a percentage (“wt %”) of the combined dry weight of all lipids of a composition (e.g., the combined dry weight of all lipids present in a liposomal composition). 
     In embodiments of the pharmaceutical compositions described herein, a compound as described herein (e.g., a compound of Formula (A), such as any of Formulae (I)-(VII) or any one of Compounds 1-63) is present in an amount that is about 0.5 wt % to about 30 wt % (e.g., about 0.5 wt % to about 20 wt %) of the combined dry weight of all lipids present in a composition (e.g., a liposomal composition). 
     In embodiments, a compound as described herein (e.g., a compound of Formula (A), such as any of Formulae (I)-(VH) or any one of Compounds 1-63) is present in an amount that is about 1 wt % to about 30 wt %, about 1 wt % to about 20 wt %, about 1 wt % to about 15 wt %, about 1 wt % to about 10 wt %, or about 5 wt % to about 25 wt % of the combined dry weight of all lipids present in a composition (e.g., a liposomal composition). In embodiments, a compound as described herein (e.g., a compound of Formula (A), such as any of Formulae (I)-(VII) or any one of Compounds 1-63) is present in an amount that is about 0.5 wt % to about 5 wt %, about 1 wt % to about 10 wt %, about 5 wt % to about 20 wt %, or about 10 wt % to about 20 wt % of the combined molar amounts of all lipids present in a composition such as a liposomal delivery vehicle. 
     In embodiments, the amount of a compound as described herein (e.g., a compound of Formula (A), such as any of Formulae (I)-(VII) or any one of Compounds 1-63) is present in an amount that is at least about 5 wt %, about 10 wt %, about 15 wt %, about 20 wt %, about 25 wt %, about 30 wt %, about 35 wt %, about 40 wt %, about 45 wt %, about 50 wt %, about 55 wt %, about 60 wt %, about 65 wt %, about 70 wt %, about 75 wt %, about 80 wt %, about 85 wt %, about 90 wt %, about 95 wt %, about 96 wt %, about 97 wt %, about 98 wt %, or about 99 wt % cf the combined dry weight of total lipids in a composition (e.g., a liposomal composition). 
     In embodiments, the amount of a compound as described herein ((e.g., a compound of Formula (A), such as any of Formulae (I)-(VII) or any one of Compounds 1-63) is present in an amount that is no more than about 5 wt %, about 10 wt %, about 15 wt %, about 20 wt %, about 25 wt %, about 30 wt %, about 35 wt %, about 40 wt %, about 45 wt %, about 50 wt %, about 55 wt %, about 60 wt %, about 65 wt %, about 70 wt %, about 75 wt %, about 80 wt %, about 85 wt %, about 90 wt %, about 95 wt %, about 96 wt %, about 97 wt %, about 98 wt %, or about 99 wt % of the combined dry weight of total lipids in a composition (e.g., a liposomal composition). 
     In embodiments, a composition (e.g., a liposomal delivery vehicle such as a lipid nanoparticle) comprises about 0.1 wt % to about 20 wt % (e.g., about 0,1 wt % to about 15 wt %) of a compound described herein (e.g., a compound of Formula (A), such as any of Formulae (I)-(VII) or any one of Compounds 1-63). In embodiments, a delivery vehicle (e.g., a liposomal delivery vehicle such as a lipid nanoparticle) comprises about 0.5 wt %, about 1 wt %, about 3 wt %, about 5 wt %, or about 10 wt % of a compound described herein (e.g., a compound of Formula (A), such as any of Formulae (I)-(VII) or any one of Compounds 1-63). In embodiments, a delivery vehicle (e.g., a liposomal delivery vehicle such as a lipid nanoparticle) comprises up to about 0.5 wt %, about 1 wt %, about 3 wt %, about 5 wt %, about 10 wt %, about 15 wt %, or about 20 wt % of a compound described herein (e.g., a compound of Formula (A), such as any of Formulae (I)-(VII) or any one of Compounds 1-63). In embodiments, the percentage results in an improved beneficial effect (e.g., improved delivery to targeted tissues such as the liver or the lung). 
     The amount of a compound as described herein (e.g., a compound of Formula (A), such as any of Formulae (I)-(VII) or any one of Compounds 1-63) in a composition also can be described as a percentage (“mol %”) of the combined molar amounts of total lipids of a composition (e.g., the combined molar amounts of all lipids present in a liposomal delivery vehicle). 
     In embodiments of pharmaceutical compositions described herein, a compound as described herein (e.g., a compound of Formula (A), such as any of Formulae (I)-(VII) or any one of Compounds 1-63) is present in an amount that is about 0.5 mol % to about 30 mol % (e.g., about 0.5 mol % to about 20 mol %) of the combined molar amounts of all lipids present in a composition such as a liposomal delivery vehicle. 
     In embodiments, a compound as described herein (e.g., a compound of Formula (A), such as any of Formulae (I)-(VII) or any one of Compounds 1-63) is present in an amount that is about 0.5 mol % to about 5 mol %, about 1 mol % to about 10 mol %, about 5 mol % to about 20 mol %, or about 10 mol % to about 20 mol % of the combined molar amounts of all lipids present in a composition such as a liposomal delivery vehicle. In embodiments, a compound as described herein (e.g., a compound of Formula (A), such as any of Formulae (I)-(VII) or any one of Compounds 1-63) is present in an amount that is about 1 mol % to about 30 mol %, about 1 mol % to about 20 mol %, about 1 mol % to about 15 mol %, about 1 mol % to about 10 mol %, or about 5 mol % to about 25 mol % of the combined dry weight of all lipids present in a composition such as a liposomal delivery vehicle 
     In certain embodiments, a compound as described herein (e.g., a compound of Formula (A), such as any of Formulae (I)-(VII) or any one cf Compounds 1-63) can comprise from about 0.1 mol % to about 50 mol %, or from 0.5 mol % to about 50 mol %, or from about 1 mol % to about 25 mol %, or from about 1 mol % to about 10 mol % of the total amount of lipids in a composition (e.g., a liposomal delivery vehicle). 
     In certain embodiments, a compound as described herein (e.g., a compound of Formula (A), such as any of Formulae (I)-(VII) or any one of Compounds 1-63) can comprise greater than about 0.1 mol %, or greater than about 0.5 mol %, or greater than about 1 mol %, or greater than about 5 mol % of the total amount of lipids in the lipid nanoparticle. 
     In certain embodiments, a compound as described (e.g., a compound of Formula (A), such as any of Formulae (1)-(VII) or any one of Compounds 1-63) can comprise less than about 25 mol %, or less than about 10 mol %, or less than about 5 mol %, or less than about 1 mol % of the total amount of lipids in a composition (e.g., a liposomal delivery vehicle). 
     In embodiments, the amount of a compound as described herein (e.g., a compound of Formula (A), such as any of Formulae (I)-(VII) or any one of Compounds 1-63) is present in an amount that is at least about 5 mol %, about 10 mol %, about 15 mol %, about 20 mol %, about 25 mol %, about 30 mol %, about 35 mol %, about 40 mol %, about 45 mol %, about 50 mol %, about 55 mol %, about 60 mol %, about 65 mol %, about 70 mol %, about 75 mol %, about 80 mol %, about 85 mol %, about 90 mol %, about 95 mol %, about 96 mol %, about 97 mol %, about 98 mol %, or about 99 mol % of the combined dry weight of total lipids in a composition (e.g., a liposomal composition). 
     In embodiments, the amount of a compound as described herein (e.g., a compound of Formula (A), such as any of Formulae (I)-(VII) or any one cf Compounds 1-63) is present in an amount that is no more than about 5 mol %, about 10 mol %, about 15 mcl %, about 20 mol %, about 25 mol %, about 30 mol %, about 35 mol %, about 40 mol %, about 45 mol %, about 50 mol %, about 55 mol %, about 60 mol %, about 65 mol %, about 70 mol %, about 75 mol %, about 80 mol %, about 85 mol %, about 90 mol %, about 95 mol %, about 96 mol %, about 97 mol %, about 98 mol %, or about 99 mol % of the combined dry weight of total lipids in a composition (e.g., a liposomal composition). 
     In embodiments, the percentage results in an improved beneficial effect (e.g., improved delivery to targeted tissues such as the liver or the lung). 
     In embodiments, a composition further comprises one more lipids (e.g., one more lipids selected from the group consisting of one or more cationic lipids, one or more non-cationic lipids, one or more cholesterol-based lipids, and one or more PEG-modified lipids). 
     In certain embodiments, such pharmaceutical (e.g., liposomal) compositions comprise one or more of a PEG-modified lipid, a non-cationic lipid and a cholesterol lipid. In embodiments, such pharmaceutical (e.g., liposomal) compositions comprise: one or more PEG-modified lipids; one or more non-cationic lipids; and one or more cholesterol lipids. In embodiments, such pharmaceutical (e.g., liposomal) compositions comprise: one or more PEG-modified lipids and one or more cholesterol lipids. 
     n embodiments, a composition (e.g., lipid nanoparticle) that encapsulates a nucleic acid (e.g., mRNA encoding a peptide or protein) comprises one or more compounds as described herein (e.g., a compound of Formula (A), such as any of Formulae (I)-(VII) or any one of Compounds 1-63) and one or more lipids selected from the group consisting of a cationic lipid, a non-cationic lipid, and a PEGylated lipid. 
     In embodiments, a composition (e.g., lipid nanoparticle) that encapsulates a nucleic acid (e.g., mRNA encoding a peptide or protein) comprises one or more compound as described herein (e.g., a compound of Formula (A), such as any of Formulae (I)-(VII) or any one of Compounds 1-63); one or more lipids selected from the group consisting of a cationic lipid, a non-cationic lipid, and a PEGylated lipid; and further comprises a cholesterol-based lipid. 
     In embodiments, a lipid nanoparticle that encapsulates a nucleic acid (e.g., mRNA encoding a peptide or protein) comprises one or more compound as described herein ((e.g., a compound of Formula (A), such as any of Formulae (I)-(VII) or any one of Compounds 1-63), as well as one or more lipids selected from the group consisting of a cationic lipid, a non-cationic lipid, a PEGylated lipid, and a cholesterol-based lipid. 
     According to various embodiments, the selection of cationic lipids, non-cationic lipids and/or PEG-modified lipids which comprise the lipid nanoparticle, as well as the relative molar ratio of such lipids to each other, is based upon the characteristics of the selected lipid(s), the nature of the intended target cells, the characteristics of the mRNA to be delivered. Additional considerations include, for example, the saturation of the alkyl chain, as well as the size, charge, pH, pKa, fusogenicity and toxicity of the selected lipid(s). Thus, the molar ratios may be adjusted accordingly. 
     Cationic Lipids 
     In addition to any of the compounds as described herein (e.g., a compound of Formula (A), such as any of Formulae (I)-(VII) or any one of Compounds 1-63), a composition may comprise one or more additional cationic lipids. 
     n some embodiments, liposomes may comprise one or more additional cationic lipids. As used herein, the phrase “cationic lipid” refers to any of a number of lipid species that have a net positive charge at a selected pH, such as physiological pH. Several cationic lipids have been described in the literature, many of which are commercially available. 
     Suitable additional cationic lipids for use in the compositions include the cationic lipids as described in international Patent Publication WO 2010/144740, which is incorporated herein by reference. In certain embodiments, the compositions include a cationic lipid, (6Z,9Z,28Z,31Z)-heptatriaconta-6,9,28,31-tetraen-19-yl 4-(dimethylamino) butanoate, having a compound structure of: 
     
       
         
         
             
             
         
       
     
     and pharmaceutically acceptable salts thereof. 
     Other suitable additional cationic lipids for use in the compositions include ionizable cationic lipids as described in International Patent Publication WO 2013/149140, which is incorporated herein by reference. In some embodiments, the compositions include a cationic lipid of one of the following formulas: 
     
       
         
         
             
             
         
       
     
     or a pharmaceutically acceptable salt thereof, wherein R 1  and R 2  are each independently selected from the group consisting of hydrogen, an optionally substituted, variably saturated or unsaturated C 1 -C 20  alkyl and an optionally substituted, variably saturated or unsaturated C 6 -C 20  acyl; wherein L 1  and L 2  are each independently selected from the group consisting of hydrogen, an optionally substituted C 1 -C 30  alkyl, an optionally substituted variably unsaturated C 1 -C 30  alkenyl, and an optionally substituted C 1 -C 30  alkynyl; wherein m and o are each independently selected from the group consisting of zero and any positive integer (e.g., where m is three); and wherein n is zero or any positive integer (e.g., where n is one). In certain embodiments, the compositions include the cationic lipid (15Z, 18Z-N,N-dimethyl-6-(9Z,12Z)-octadeca-9,12-dien-1-yl) tetracosa-15,18-dien-1-amine (“HGT5000”), having a compound structure of: 
     
       
         
         
             
             
         
       
     
     and pharmaceutically acceptable salts thereof. In certain embodiments, the compositions include the cationic lipid (15Z, 18Z)-N,N-dimethyl-6-((9Z,12Z)-octadeca-9,12-dien-1-yl) tetracosa-4,15,18-trien-1-amine (“HGT5001”), having a compound structure of: 
     
       
         
         
             
             
         
       
     
     and pharmaceutically acceptable salts thereof. In certain embodiments, the include the cationic lipid and (15Z,18Z)-N,N-dimethyl-6-((9Z,12Z)-octadeca-9,12-dien-1-yl) tetracosa-5,15,18-trien-1-amine (“HGT5002”), having a compound structure of: 
     
       
         
         
             
             
         
       
     
     and pharmaceutically acceptable salts thereof, 
     Other suitable additional cationic lipids for use in the compositions include cationic lipids described as aminoalcohol lipidoids in International Patent Publication WO 2010/053572, which is incorporated herein by reference. In certain embodiments, the compositions include a cationic lipid having a compound structure of: 
     
       
         
         
             
             
         
       
     
     and pharmaceutically acceptable salts thereof. 
     Other suitable additional cationic lipids for use in the compositions include the cationic lipids as described in International Patent Publication WO 2016/118725, which is incorporated herein by reference. In certain embodiments, the compositions include a cationic lipid having a compound structure of: 
     
       
         
         
             
             
         
       
     
     and pharmaceutically acceptable salts thereof. 
     Other suitable additional cationic lipids for use in the compositions include the cationic lipids as described in International Patent Publication WO 2016/118724, which is incorporated herein by reference. In certain embodiments, the compositions include a cationic lipid having a compound structure of: 
     
       
         
         
             
             
         
       
     
     and pharmaceutically acceptable salts thereof. 
     Other suitable cationic lipids for use in the compositions include a cationic lipid having the formula of 14,25-ditridecyl 15,18,21,24-tetraaza-octatriacontane, and pharmaceutically acceptable salts thereof. 
     Other suitable additional cationic lipids for use in the compositions include the cationic lipids as described in International Patent Publications WO 2013/063468 and WO 2016/205691, each of which are incorporated herein by reference. In some embodiments, the compositions include a cationic lipid of the following formula: 
     
       
         
         
             
             
         
       
     
     or pharmaceutically acceptable salts thereof, wherein each instance of R L  is independently optionally substituted C 6 -C 40  alkenyl. In certain embodiments, the compositions include a cationic lipid having a compound structure of: 
     
       
         
         
             
             
         
       
     
     and pharmaceutically acceptable salts thereof. 
     In certain embodiments, the compositions include a cationic lipid having a compound structure of: 
     
       
         
         
             
             
         
       
     
     and pharmaceutically acceptable salts thereof. 
     In certain embodiments, the compositions include a cationic lipid having a compound structure of: 
     
       
         
         
             
             
         
       
     
     and pharmaceutically acceptable salts thereof. 
     In certain embodiments, the compositions include a cationic lipid having a compound structure of: 
     
       
         
         
             
             
         
       
     
     and pharmaceutically acceptable salts thereof. 
     Other suitable additional cationic lipids for use in the compositions include the cationic lipids as described in International Patent Publication WO 2015/184256, which is incorporated herein by reference. In some embodiments, the compositions include a cationic lipid of the following formula: 
     
       
         
         
             
             
         
       
     
     or a pharmaceutically acceptable salt thereof, wherein each X independently is O or S; each Y independently is O or S; each m independently is 0 to 20; each n independently is 1 to 6; each R A  is independently hydrogen, optionally substituted C1-50 alkyl, optionally substituted C2-50 alkenyl, optionally substituted C2-50 alkynyl, optionally substituted C3-10 carbocyclyl, optionally substituted 3-14 membered heterocyclyl, optionally substituted C6-14 aryl, optionally substituted 5-14 membered heteroaryl or halogen; and each R B  is independently hydrogen, optionally substituted C1-50 alkyl, optionally substituted C2-50 alkenyl, optionally substituted C2-50 alkynyl, optionally substituted C3-10 carbocyclyl, optionally substituted 3-14 membered heterocyclyl, optionally substituted C6-14 aryl, optionally substituted 5-14 membered heteroaryl or halogen. In certain embodiments, the compositions include a cationic lipid, “Target 23”, having a compound structure of: 
     
       
         
         
             
             
         
       
     
     and pharmaceutically acceptable salts thereof. 
     Other suitable additional cationic lipids for use in the compositions include the cationic lipids as described in International Patent Publication WO 2016/004202, which is incorporated herein by reference. In some embodiments, the compositions include a cationic lipid having the compound structure: 
     
       
         
         
             
             
         
       
     
     or a pharmaceutically acceptable salt thereof. 
     In some embodiments, the compositions include a cationic lipid having the compound structure: 
     
       
         
         
             
             
         
       
     
     or a pharmaceutically acceptable salt thereof. 
     In some embodiments, the compositions include a cationic lipid having the compound structure: 
     
       
         
         
             
             
         
       
     
     or a pharmaceutically acceptable salt thereof. 
     Other suitable additional cationic lipids for use in the compositions include the cationic lipids as described in J. McClellan, M. C. King, Cell 2010, 141, 210-217 and in Whitehead et al., Nature Communications (2014) 5:4277, which is incorporated herein by reference. In certain embodiments, the cationic lipids of the compositions include a cationic lipid having a compound structure of: 
     
       
         
         
             
             
         
       
     
     and pharmaceutically acceptable salts thereof, 
     Other suitable additional cationic lipids for use in the compositions include the cationic lipids as described in International Patent Publication WO 2015/199952, which is incorporated herein by reference. In some embodiments, the compositions include a cationic lipid having the compound structure: 
     
       
         
         
             
             
         
       
     
     and pharmaceutically acceptable salts thereof. 
     In some embodiments, the compositions include a cationic lipid having the compound structure: 
     
       
         
         
             
             
         
       
     
     and pharmaceutically acceptable salts thereof. 
     In some embodiments, the compositions include a cationic lipid having the compound structure: 
     
       
         
         
             
             
         
       
     
     and pharmaceutically acceptable salts thereof. 
     In some embodiments, the compositions include a cationic lipid having the compound structure: 
     
       
         
         
             
             
         
       
     
     and pharmaceutically acceptable salts thereof. 
     In some embodiments, the compositions include a cationic lipid having the compound structure: 
     
       
         
         
             
             
         
       
     
     and pharmaceutically acceptable salts thereof. 
     In some embodiments, the compositions include a cationic lipid having the compound structure: 
     
       
         
         
             
             
         
       
     
     and pharmaceutically acceptable salts thereof, 
     In some embodiments, the compositions include a cationic lipid having the compound structure: 
     
       
         
         
             
             
         
       
     
     and pharmaceutically acceptable salts thereof. 
     In some embodiments, the compositions include a cationic lipid having the compound structure: 
     
       
         
         
             
             
         
       
     
     and pharmaceutically acceptable salts thereof. 
     In some embodiments, the compositions include a cationic lipid having the compound structure: 
     
       
         
         
             
             
         
       
     
     and pharmaceutically acceptable salts thereof. 
     In some embodiments, the compositions include a cationic lipid having the compound structure: 
     
       
         
         
             
             
         
       
     
     and pharmaceutically acceptable salts thereof. 
     In some embodiments, the compositions include a cationic lipid having the compound structure: 
     
       
         
         
             
             
         
       
     
     and pharmaceutically acceptable salts thereof. 
     In some embodiments, the compositions include a cationic lipid having the compound structure: 
     
       
         
         
             
             
         
       
     
     and pharmaceutically acceptable salts thereof. 
     In some embodiments, the compositions include a cationic lipid having the compound structure: 
     
       
         
         
             
             
         
       
     
     and pharmaceutically acceptable salts thereof. 
     Other suitable additional cationic lipids for use in the compositions include the cationic lipids as described in International Patent Publication WO 2017/004143, which is incorporated herein by reference. 
     In some embodiments, the compositions include a cationic lipid having the compound structure: 
     
       
         
         
             
             
         
       
     
     and pharmaceutically acceptable salts thereof. 
     In some embodiments, the compositions include a cationic lipid having the compound structure: 
     
       
         
         
             
             
         
       
     
     and pharmaceutically acceptable salts thereof. 
     In some embodiments, the compositions include a cationic lipid having the compound structure: 
     
       
         
         
             
             
         
       
     
     and pharmaceutically acceptable salts thereof, 
     In some embodiments, the compositions include a cationic lipid having the compound structure: 
     
       
         
         
             
             
         
       
     
     and pharmaceutically acceptable salts thereof. 
     In some embodiments, the compositions include a cationic lipid having the compound structure: 
     
       
         
         
             
             
         
       
     
     and pharmaceutically acceptable salts thereof. 
     In some embodiments, the compositions include a cationic lipid having the compound structure: 
     
       
         
         
             
             
         
       
     
     and pharmaceutically acceptable salts thereof. 
     In some embodiments, the compositions include a cationic lipid having the compound structure: 
     
       
         
         
             
             
         
       
     
     and pharmaceutically acceptable salts thereof. 
     In some embodiments, the compositions include a cationic lipid having the compound structure: 
     
       
         
         
             
             
         
       
     
     and pharmaceutically acceptable salts thereof. 
     In some embodiments, the compositions include a cationic lipid having the compound structure: 
     
       
         
         
             
             
         
       
     
     and pharmaceutically acceptable salts thereof. 
     In some embodiments, the compositions include a cationic lipid having the compound structure: 
     
       
         
         
             
             
         
       
     
     and pharmaceutically acceptable salts thereof. 
     In some embodiments, the compositions include a cationic lipid having the compound structure: 
     
       
         
         
             
             
         
       
     
     and pharmaceutically acceptable salts thereof, 
     In some embodiments, the compositions include a cationic lipid having the compound structure: 
     
       
         
         
             
             
         
       
     
     and pharmaceutically acceptable salts thereof. 
     In some embodiments, the compositions include a cationic lipid having the compound structure: 
     
       
         
         
             
             
         
       
     
     and pharmaceutically acceptable salts thereof, 
     In some embodiments, the compositions include a cationic lipid having the compound structure: 
     
       
         
         
             
             
         
       
     
     and pharmaceutically acceptable salts thereof. 
     In some embodiments, the compositions include a cationic lipid having the compound structure: 
     
       
         
         
             
             
         
       
     
     and pharmaceutically acceptable salts thereof. 
     In some embodiments, the compositions include a cationic lipid having the compound structure: 
     
       
         
         
             
             
         
       
     
     and pharmaceutically acceptable salts thereof, 
     In some embodiments, the compositions include a cationic lipid having the compound structure: 
     
       
         
         
             
             
         
       
     
     and pharmaceutically acceptable salts thereof. 
     Other suitable additional cationic lipids for use in the compositions include the cationic lipids as described in International Patent Publication WO 2017/075531, which is incorporated herein by reference. In some embodiments, the compositions include a cationic lipid of the following formula: 
     
       
         
         
             
             
         
       
     
     or a pharmaceutically acceptable salt thereof, wherein one of L 1  or L 2  is —O(C═O)—, —(C═O)O—, —C(═O)—, —O—, —S(O) x , —S—S—, —C(═O)S—, —SC(═O)—, —NR a C(═O)—, —C(═O)NR a —, NR a C(═O)NR a —, —OC(═O)NR a —, or —NR a C(═O)O—; and the other of L 1  or L 2  is —O(C═O)—, —(C═O)O—, —C(═O)—, —O—, —S(O) x , —S—S—, —C(═O)S—, SC(═O)—, —NR a C(═O)—, —C(═O)NR a —, NR a C(═O(NR a , —OC(═O)NR a — or —NR a C(═O)O— or a direct bond; G 1  and G 2  are each independently unsubstituted C 1 -C 12  alkylene or C 1 -C 12 alkenylene; G 3  is C 1 -C 24  alkylene, C 1 -C 24 alkenylene, C 3 -C 8  cycloalkylene, C 3 -C 8  cycloalkenylene; R a  is H or C 1 -C 12  alkyl; R 1  and R 2  are each independently C 6 -C 24  alkyl or C 6 -C 24  alkenyl; R 3  is H, OR 5 , CN, —C(O)OR 4 , —OC(═O)R 4  or —NR 5 C(═O)R 4 ; R 4  is C 1 -C 12  alkyl; R 5  is H or C 1 -C 6  alkyl; and x is 0, 1 or 2. 
     Other suitable additional cationic lipids for use in the compositions include the cationic lipids as described in International Patent Publication WO 2017/117528, which is incorporated herein by reference. In some embodiments, the compositions include a cationic lipid having the compound structure: 
     
       
         
         
             
             
         
       
     
     and pharmaceutically acceptable salts thereof. 
     In some embodiments, the compositions include a cationic lipid having the compound structure: 
     
       
         
         
             
             
         
       
     
     and pharmaceutically acceptable salts thereof. 
     In some embodiments, the compositions include a cationic lipid having the compound structure: 
     
       
         
         
             
             
         
       
     
     and pharmaceutically acceptable salts thereof. 
     Other suitable additional cationic lipids for use in the compositions include the cationic lipids as described in International Patent Publication WO 2017/049245, which is incorporated herein by reference. In some embodiments, the cationic lipids of the compositions and methods of the present invention include a compound of one of the following formulas: 
     
       
         
         
             
             
         
       
     
     and pharmaceutically acceptable salts thereof. For any one of these four formulas, R4 is independently selected from —(CH 2 ) n Q and —(CH 2 ) n CHQR; Q is selected from the group consisting of —OR, —OH, —O(CH 2 ) n N(R) 2 , —OC(O)R, —CX 3 , —CN, —N(R)C(O)R, —N(H)C(O)R, —N(R)S(O) 2 R, —N(H)S(O) 2 R, —N(R)S(O)N(R) 2 , —N(H)C(O)N(R) 2 , —N(H)C(O)N(H)(R), —N(R)C(S)N(R) 2 , —N(H)C(S)N(R) 2 , —N(H)C(S)N(H)(R), and a heterocycle; R is independently selected from the group consisting of C 1-3  alkyl, C 2-3  alkenyl, and H; and n is 1, 2, or 3. 
     In certain embodiments, the compositions include a cationic lipid having a compound structure of: 
     
       
         
         
             
             
         
       
     
     and pharmaceutically acceptable salts thereof. 
     In certain embodiments, the compositions include a cationic lipid having a compound structure of: 
     
       
         
         
             
             
         
       
     
     and pharmaceutically acceptable salts thereof, 
     In certain embodiments, the compositions include a cationic lipid having a compound structure of: 
     
       
         
         
             
             
         
       
     
     and pharmaceutically acceptable salts thereof. 
     In certain embodiments, the compositions include a cationic lipid having a compound structure of: 
     
       
         
         
             
             
         
       
     
     and pharmaceutically acceptable salts thereof. 
     Other suitable additional cationic lipids for use in the compositions include the cationic lipids as described in International Patent Publication WO 2017/173054 and WO 2015/095340, each of which is incorporated herein by reference. 
     In certain embodiments, the compositions include a cationic lipid having a compound structure of: 
     
       
         
         
             
             
         
       
     
     and pharmaceutically acceptable salts thereof. 
     In certain embodiments, the compositions include a cationic lipid having a compound structure of: 
     
       
         
         
             
             
         
       
     
     and pharmaceutically acceptable salts thereof. 
     In certain embodiments, the compositions include a cationic lipid having a compound structure of: 
     
       
         
         
             
             
         
       
     
     and pharmaceutically acceptable salts thereof. 
     In certain embodiments, the compositions include a cationic lipid having a compound structure of: 
     
       
         
         
             
             
         
       
     
     and pharmaceutically acceptable salts thereof. 
     Other suitable additional cationic lipids for use in the compositions include cholesterol-based cationic lipids. In certain embodiments, the compositions include imidazole cholesterol ester or “ICE”, having a compound structure of: 
     
       
         
         
             
             
         
       
     
     and pharmaceutically acceptable salts thereof. 
     Other suitable additional cationic lipids for use in the compositions include cleavable cationic lipids as described in International Patent Publication WO 2012/170889, which is incorporated herein by reference. In some embodiments, the compositions include a cationic lipid of the following formula: 
     
       
         
         
             
             
         
       
     
     wherein R 1  is selected from the group consisting of imidazole, guanidinium, amino, imine, enamine, an optionally-substituted alkyl amino (e.g., an alkyl amino such as dimethylamino) and pyridyl; wherein R 2  is selected from the group consisting of one of the following two formulas: 
     
       
         
         
             
             
         
       
     
     and wherein R 3  and R 4  are each independently selected from the group consisting of an optionally substituted, variably saturated or unsaturated C 6 -C 2  alkyl and an optionally substituted, variably saturated or unsaturated C 6 -C 2  acyl; and wherein n is zero or any positive integer (e.g., one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, twenty or more). 
     In certain embodiments, the compositions include a cationic lipid, “HGT4002”, having a compound structure of: 
     
       
         
         
             
             
         
       
     
     and pharmaceutically acceptable salts thereof. 
     In certain embodiments, the compositions include a cationic lipid, “HGT4002”, having a compound structure of: 
     
       
         
         
             
             
         
       
     
     and pharmaceutically acceptable salts thereof. 
     In certain embodiments, the compositions include a cationic lipid, “HGT4003”, having a con-mound structure of: 
     
       
         
         
             
             
         
       
     
     and pharmaceutically acceptable salts thereof. 
     In certain embodiments, the compositions include a cationic lipid, “HGT4004”, having a compound structure of: 
     
       
         
         
             
             
         
       
     
     and pharmaceutically acceptable salts thereof, 
     In certain embodiments, the compositions include a cationic lipid “HGT4005”, having a compound structure of: 
     
       
         
         
             
             
         
       
     
     and pharmaceutically acceptable salts thereof. 
     In some embodiments, the compositions include the cationic lipid, N-[1-(2,3-dioleyloxy)propyl]-N,N,N-trimethylammonium chloride (“DOTMA”). Feigner et al. (Proc. Nat&#39;l Acad. Sci. 84, 7413 (1987); U.S. Pat. No. 4,897,355, each of which is incorporated herein by reference. DOTMA can be formulated alone or can be combined with a neutral lipid (e.g., dioleoylphosphatidyl-ethanolamine or “DOPE”) or still other cationic or non-cationic lipids into a liposomal transfer vehicle or a lipid nanoparticle, and such liposomes can be used to enhance the delivery of nucleic acids into target cells. Other cationic lipids suitable for the compositions include, for example, 5-carboxyspermylglycinedioctadecylamide (“DOGS”); 2,3-dioleyloxy-N-[2(spermine-carboxamido)ethyl]-N,N-dimethyl-1-propanaminium (“DOSPA”) (Behr et al. Proc. Nat&#39;l Acad. Sci. 86, 6982 (1989), U.S. Pat. Nos. 5,171,678; 5,334,761); 1,2-Dioleoyl-3-Dimethylammonium-Propane (“DODAP”); 1,2-Dioleoyl-3-Trimethylammonium-Propane (“DOTAP”). 
     Additional exemplary cationic lipids suitable for the compositions also include: 1,2-distearyloxy-N,N-dimethyl-3-aminopropane (“DSDMA”); 1,2-dioleyloxy-N,N-dimethyl-3-aminopropane (“DODMA”); 1,2-dilinoleyloxy-N,N-dimethyl-3-aminopropane (“DLinDMA”); 1,2-dilinolenyloxy-N,N-dimethyl-3-aminopropane (“DLenDMA”); N-dioleyl-N,N-dimethylammonium chloride (“DODAC”); N,N-distearyl-N,N-dimethylammonium bromide (“DDAB”); N-(1,2-dimyristyloxyprop-3-yl)-N,N-dimethyl-N-hydroxyethyl ammonium bromide (“DMRIE”); 3-dimethylamime-2-(cholest-5-en-3-beta-oxybutan-4-oxy)-1-(cis,cis-9,12-octadecadienoxy)propane (“CLinDMA”); 2-[5′-(cholest-5-en-3-beta-oxy)-3′-oxapentoxy)-3-dimethyl-2′-octadecadienoxy)propane (“CpLinDMA”); N,N-dimethyl-3,4-dioleyloxybenzylamine (“DMOBA”); 1,2-N,N′-dioleylcarbamyl-3-dimethylaminopropane (“DOcarbDAP”); 2,3-Dilinoleoyloxy-N,N-dimethylpropylamine (“DLinDAP”); 1,2-N,N′-Dilinoleylcarbamyl-3-dimethylaminopropane (“DLincarbDAP”); 1,2-Dilinoleoylcarbamyl-3-dimethylaminopropane (“DLinCDAP”); 2,2-dilinoleyl-4-dimethylaminomethyl-[1,3]-dioxolane (“DLin-K-DMA”); 2-((8-[(3P)-cholest-5-en-3-yloxy]octyl)oxy)-N,N-dimethyl-3-[(9Z, 12Z)-octadeca-9,12-digin-1-yloxy]propane-1-amine (“Octyl-CLinDMA”); (2R)-2-((8-[(3beta)-cholest-5-en-3-yloxy]octyl)oxy)-N, N-dimethyl-3-[(9Z, 12Z)-octadeca-9, 12-dien-1-yloxy]propan-1-amine (“Octyl-CLinDMA (2R)”); (25)-2-((8-[(3P)-cholest-5-en-3-yloxy]octyl)oxy)-N, fsl-dimethyh3-[(9Z, 12Z)-octadeca-9, 12-dien-1-yloxy]propan-1-amine (“Octyl-CLinDIMA (2S)”); 2,2-dilinoleyl-4-dimethylaminoethyl-[1,3]-dioxolane (“DLin-K-XTC2-DMA”); and 2-(2,2-di((9Z,12Z)-octadeca-9,12-dien-1-yl)-1,3-dioxolan-4-yl)-N,N-dimethylethanamine (“DLin-KC2-DMA”) (see, WO 2010/042877, which is incorporated herein by reference; Semple et al., Nature Biotech. 28: 172-176 (2010)). (Heyes, J., et al., J Controlled Release 107: 276-287 (2005); Morrissey, D V., et al., Nat. Biotechnol. 23(8): 1003-1007 (2005); International Patent Publication WO 2005/121348). In some embodiments, one or more of the cationic lipids comprise at least one of an imidazole, dialkylamino, or guanidinium moiety. 
     In some embodiments, one or more cationic lipids suitable for the compositions include 2,2-Dilinoleyl-4-dimethylaminoethyl-[1,3]-dioxolane (“XTC”); (3aR,5s,6aS)-N,N-dimethyl-2,2-di((9Z,12Z)-octadeca-9,12-dienyl)tetrahydro-3aH-cyclopenta[d] [1 ,3]dioxol-5-amine (“ALNY-100”) and/or 4,7,13-tris(3-oxo-3-(undecylamino)propyl)-N1,N16-diundecyl,-4,7,10,13-tetraazahexadecane-1,16-diamide (“NC98-5”). 
     In some embodiments, the compositions include one or more cationic lipids that constitute at least about 5%, 10%, 20%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, or 70%, measured by weight, of the total lipid content in the composition, e.g., a lipid nanoparticle. In some embodiments, the compositions include one or more cationic lipids that constitute at least about 5%, 10%, 20%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, or 70%, measured as a mol %, of the total lipid content in the composition, e.g., a lipid nanoparticle. In some embodiments, the compositions include one or more cationic lipids that constitute about 30-70% (e.g., about 30-65%, about 30-60%, about 30-55%, about 30-50%, about 30-45%, about 30-40%, about 35-50%, about 35-45%, or about 35-40%), measured by weight, of the total lipid content in the composition, e.g., a lipid nanoparticle. In some embodiments, the compositions include one or more cationic lipids that constitute about 30-70% (e.g., about 30-65%, about 30-60%, about 30-55%, about 30-50%, about 30-45%, about 30-40%, about 35-50%, about 35-45%, or about 35-40%), measured as mel %, of the total lipid content in the composition, e.g., a lipid nanoparticle. 
     Helper Lipids 
     Compositions (e.g., liposomal compositions) may also comprise one or more helper lipids. Such helper lipids include non-cationic lipids. As used herein, the phrase “non-cationic lipid” refers to any neutral, zwitterionic or anionic lipid. As used herein, the phrase “anionic lipid” refers to any of a number of lipid species that carry a net negative charge at a selected pH, such as physiological pH. Non-cationic lipids include, but are not limited to, distearoylphosphatidylcholine (DSPC), dioleoylphosphatidylcholine (DOPC), dipalmitoylphosphatidylcholine (DPPC), dioleoylphosphatidylglycerol (DOPG), dipalmitoylphosphatidylglycerol (DPPG), dioleoylphosphatidylethanolamine (DOPE), palmitoyloleoylphosphatidylcholine (POPC), palmitoyloleoyl-phosphatidylethanolamine (POPE), dioleyl-phosphatidylethanolamine 4-(N-maleimidomethyl)-cyclohexane-1-carboxylate (DOPE-mal), dipalmitoyl phosphatidyl ethanolamine (DPPE), dimyristoylphosphoethanolamine (DMPE), distearoyl-phosphatidyl-ethanolamine (DPSE), 16-O-monomethyl PE, 16-O-dimethyl PE, 18-1-trans PE, 1-stearoyl-2-oleoyl-phosphatidyethanolamine (SOPE), or a mixture thereof. In embodiments, a non-cationic or helper lipid is dioleoylphosphatidylethanolamine (DOPE). 
     In some embodiments, a non-cationic lipid is a neutral lipid, i.e., a lipid that does not carry a net charge in the conditions under which the composition is formulated and/or administered. 
     In some embodiments, a non-cationic lipid may be present in a molar ratio (mol %) of about 5% to about 90%, about 5% to about 70%, about 5% to about 50%, about 5% to about 40%, about 5% to about 30%, about 10% to about 70%, about 10% to about 50%, or about 10% to about 40% of the total lipids present in a composition. In some embodiments, total non-cationic lipids may be present in a molar ratio (mol %) of about 5% to about 90%, about 5% to about 70%, about 5% to about 50%, about 5% to about 40%, about 5% to about 30%, about 10% to about 70%, about 10% to about 50%, or about 10% to about 40% of the total lipids present in a composition. In some embodiments, the percentage of non-cationic lipid in a liposome may be greater than about 5 mol %, greater than about 10 mol %, greater than about 20 mol %, greater than about 30 mol %, or greater than about 40 mol %. In some embodiments, the percentage total non-cationic lipids in a liposome may be greater than about 5 mol %, greater than about 10 mol %, greater than about 20 mol %, greater than about 30 mol %, or greater than about 40 mol %. In some embodiments, the percentage of non-cationic lipid in a liposome is no more than about 5 mol %, no more than about 10 mol %, no more than about 20 mol %, no more than about 30 mol %, or no more than about 40 mol %. In some embodiments, the percentage total non-cationic lipids in a liposome may be no more than about 5 mol %, no more than about 10 mol %, no more than about 20 mol %, no more than about 30 mol %, or no more than about 40 mol %. 
     In some embodiments, a non-cationic lipid may be present in a weight ratio (wt %) of about 5% to about 90%, about 5% to about 70%, about 5% to about 50%, about 5% to about 40%, about 5% to about 30%, about 10% to about 70%, about 10% to about 50%, or about 10% to about 40% of the total lipids present in a composition. In some embodiments, total non-cationic lipids may be present in a weight ratio (wt %) of about 5% to about 90%, about 5% to about 70%, about 5% to about 50%, about 5% to about 40%, about 5% to about 30%, about 10% to about 70%, about 10% to about 50%, or about 10% to about 40% of the total lipids present in a composition. In some embodiments, the percentage of non-cationic lipid in a liposome may be greater than about 5 wt %, greater than about 10 wt %, greater than about 20 wt %, greater than about 30 wt %, or greater than about 40 wt %. In some embodiments, the percentage total non-cationic lipids in a liposome may be greater than about 5 wt %, greater than about 10 wt %, greater than about 20 wt %, greater than about 30 wt %, or greater than about 40 wt %. In some embodiments, the percentage of non-cationic lipid in a liposome is no more than about 5 wt %, no more than about 10 wt %, no more than about 20 wt %, no more than about 30 wt %, or no more than about 40 wt %. In some embodiments, the percentage total non-cationic lipids in a liposome may be no more than about 5 wt %, no more than about 10 wt %, no more than about 20 wt %, no more than about 30 wt %, or no more than about 40 wt %. 
     Cholesterol-Based Lipids 
     In some embodiments, a composition (e.g., a liposomal composition) comprises one or more cholesterol-based lipids. For example, suitable cholesterol-based lipids include cholesterol and, for example, DC-Chol (N,N-dimethyl-N-ethylcarboxamidocholesterol), 1,4-bis(3-N-oleylamino-propyl)piperazine (Gao, et al, Biochem. Biophys. Res. Comm. 179, 280 (1991); Wolf et al. BioTechniques 23, 139 (1997); U.S. Pat. No. 5,744,335), or imidazole cholesterol ester (ICE), which has the following structure, 
     
       
         
         
             
             
         
       
     
     In some embodiments, a cholesterol-based lipid may be present in a molar ratio (mol %) of about 1% to about 30%, or about 5% to about 20% of the total lipids present in a liposome. In some embodiments, the percentage cf cholesterol-based lipid in the lipid nanoparticle may be greater than about 5 mol %, greater than about 10 mol %, greater than about 20 mol %, greater than about 30 mol %, or greater than about 40 mol %. In some embodiments, the percentage of cholesterol-based lipid in the lipid nanoparticle may be no more than about S mol %, no more than about 10 mol %, no more than about 20 mol %, no more than about 30 mol %, or no more than about 40 mol %. 
     In some embodiments, a cholesterol-based lipid may be present in a weight ratio (wt %) of about 1% to about 30%, or about 5% to about 20% of the total lipids present in a liposome. In some embodiments, the percentage of cholesterol-based lipid in the lipid nanoparticle may be greater than about 5 wt %, greater than about 10 wt %, greater than about 20 wt %, greater than about 30 wt %, or greater than about 40 wt %. In some embodiments, the percentage of cholesterol-based lipid in the lipid nanoparticle may be no more than about 5 wt %, no more than about 10 wt %, no more than about 20 wt %, no more than about 30 wt %, or no more than about 40 wt %. 
     PEGylated Lipids 
     In some embodiments, a composition (e.g., a liposomal composition) comprises one or more further PEGylated lipids. 
     For example, the use of polyethylene glycol (PEG)-modified phospholipids and derivatized lipids such as derivatized ceramides (PEG-CER), including N-octanoyl-sphingosine-1-[succinyl(methoxy polyethylene glycol)-2000] (CS PEG-2000 ceramide) is also contemplated by the present invention in combination with one or more of compounds described herein (e.g., a compound of Formula (A), such as any of Formulae (I)-(VII) or any one of Compounds 1-63) and, in some embodiments, other lipids together which comprise the liposome. In some embodiments, particularly useful exchangeable lipids are PEG-ceramides having shorter acyl chains (e.g., C 14  or C18). 
     Contemplated further PEG-modified lipids (also referred to herein as a PEGylated lipid, which term is interchangeable with PEG-modified lipid) include, but are not limited to, a polyethylene glycol chain of up to 5 kDa in length covalently attached to a lipid with alkyl chain(s) of C 6 -C 20  length. In some embodiments, a PEG-modified or PEGylated lipid is PEGylated cholesterol or PEG-2K. The addition of such components may prevent complex aggregation and may also provide a means for increasing circulation lifetime and increasing the delivery of the lipid-nucleic acid composition to the target cell, (Klibanov etal. (1990) FEBS Letters, 268 (1): 235-237), or they may be selected to rapidly exchange out of the formulation in vivo (see U.S. Pat. No. 5,885,613). 
     Further PEG-modified phospholipid and derivatized lipids of the present invention may be present in a molar ratio (mol %) from about 0% to about 15%, about 0.5% to about 15%, about 1% to about 15%, about 4% to about 10%, or about 2% of the total lipid present in the composition (e.g., a liposomal composition). 
     Further PEG-modified phospholipid and derivatized lipids of the present invention may be present in a weight ratio (wt %) from about 0% to about 15%, about 0.5% to about 15%, about 1% to about 15%, about 4% to about 10%, or about 2% of the total lipid present in the composition (e.g., a liposomal composition). 
     Pharmaceutical Formulations and Therapeutic Uses 
     Compounds described herein (e.g., a compound of Formula (A), such as any of Formulae (I)-(VII) or any one of Compounds 1-63) may be used in the preparation of compositions (e.g., to construct liposomal compositions) that facilitate or enhance the delivery and release of encapsulated materials (e.g., one or more therapeutic polynucleotides) to one or more target cells (e.g., by permeating or fusing with the lipid membranes of such target cells). 
     For example, when a liposomal composition (e.g., a lipid nanoparticle) comprises or is otherwise enriched with one or more of the compounds disclosed herein, the phase transition in the lipid bilayer of the one or more target cells may facilitate the delivery of the encapsulated materials (e.g., one or more therapeutic polynucleotides encapsulated in a lipid nanoparticle) into the one or more target cells. 
     Similarly, in certain embodiments compounds described herein (e.g., a compound of Formula (A), such as any of Formulae (I)-(VII) or any one of Compounds 1-63) may be used to prepare liposomal vehicles that are characterized by their reduced toxicity in vivo. In certain embodiments, the reduced toxicity is a function of the high transfection efficiencies associated with the compositions disclosed herein, such that a reduced quantity of such composition may administered to the subject to achieve a desired therapeutic response or outcome. 
     Thus, pharmaceutical formulations comprising a compound described (e.g., a compound of Formula (A), such as any of Formulae (I)-(VII) or any one of Compounds 1-63) and nucleic acids provided by the present invention may be used for various therapeutic purposes. To facilitate delivery of nucleic acids in vivo, a compound described herein (e.g., a compound of Formula (A), such as any of Formulae (I)-(VII) or any one of Compounds 1-63) and nucleic acids can be formulated in combination with one or more additional pharmaceutical carriers, targeting ligands or stabilizing reagents. In some embodiments, a compound described herein (e.g., a compound of Formula (A), such as any of Formulae (I)-(VII) or any one of Compounds 1-63) can be formulated via pre-mixed lipid solution. In other embodiments, a composition comprising a compound described herein (e.g., a compound of Formula (A), such as any of Formulae (I)-(VII) or any one of Compounds 1-63) can be formulated using post-insertion techniques into the lipid membrane of the nanoparticles. Techniques for formulation and administration of drugs may be found in “Remington&#39;s Pharmaceutical Sciences,” Mack Publishing Co., Easton, Pa., latest edition. 
     Suitable routes of administration include, for example, oral, rectal, vaginal, transmucosal, pulmonary including intratracheal or inhaled, or intestinal administration; parenteral delivery, including intradermal, transdermal (topical), intramuscular, subcutaneous, intramedullary injections, as well as intrathecal, direct intraventricular, intravenous, intraperitoneal, or intranasal. In particular embodiments, the intramuscular administration is to a muscle selected from the group consisting of skeletal muscle, smooth muscle and cardiac muscle. In some embodiments the administration results in delivery of the nucleic acids to a muscle cell. In some embodiments the administration results in delivery of the nucleic acids to a hepatocyte (i.e., liver cell). 
     Alternatively or additionally, pharmaceutical formulations of the invention may be administered in a local rather than systemic manner, for example, via injection of the pharmaceutical formulation directly into a targeted tissue, preferably in a sustained release formulation. Local delivery can be affected in various ways, depending on the tissue to be targeted. Exemplary tissues in which delivered mRNA may be delivered and/or expressed include, but are not limited to the liver, kidney, heart, spleen, serum, brain, skeletal muscle, lymph nodes, skin, and/or cerebrospinal fluid. In embodiments, the tissue to he targeted in the liver. For example, aerosols containing compositions of the present invention can be inhaled (for nasal, tracheal, or bronchial delivery); compositions of the present invention can be injected into the site of injury, disease manifestation, or pain, for example; compositions can be provided in lozenges for oral, tracheal, or esophageal application; can be supplied in liquid, tablet or capsule form for administration to the stomach or intestines, can be supplied in suppository form for rectal or vaginal application; or can even be delivered to the eye by use of creams, drops, or even injection. 
     Compositions described herein can comprise mRNA encoding peptides including those described herein (e.g., a polypeptide such as a protein). 
     In embodiments, a mRNA encodes a polypeptide. 
     in embodiments, a mRNA encodes a protein. 
     Exemplary peptides encoded by mRNA (e.g., exemplary proteins encoded by mRNA) are described herein. 
     The present invention provides methods for delivering a composition having full-length mRNA molecules encoding a peptide or protein of interest for use in the treatment of a subject, e.g., a human subject or a cell of a human subject or a cell that is treated and delivered to a human subject. 
     Accordingly, in certain embodiments the present invention provides a method for producing a therapeutic composition comprising full-length mRNA that encodes a peptide or protein for use in the delivery to or treatment of the lung of a subject or a lung cell. In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for cystic fibrosis transmembrane conductance regulator (CFTR) protein. In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for ATP-binding cassette sub-family A member 3 protein. In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for dynein axonemal intermediate chain 1 protein. In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for dynein axonemal heavy chain 5 (DNAH5) protein. In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for alpha-1-antitrypsin protein. In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for forkhead box P3 (FOXP3) protein. In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes one or more surfactant protein, e.g., one or more of surfactant A protein, surfactant B protein, surfactant C protein, and surfactant D protein. 
     In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes a peptide or protein for use in the delivery to or treatment of the liver of a subject or a liver cell. Such peptides and polypeptides can include those associated with a urea cycle disorder, associated with a lysosomal storage disorder, with a glycogen storage disorder, associated with an amino acid metabolism disorder, associated with a lipid metabolism or fibrotic disorder, associated with methylmalonic acidemia, or associated with any other metabolic disorder for which delivery to or treatment of the liver or a liver cell with enriched full-length mRNA provides therapeutic benefit. 
     In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for a protein associated with a urea cycle disorder. In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for ornithine transcarbamylase (OTC) protein. In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for arginosuccinate synthetase 1 protein. In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for carbamoyl phosphate synthetase I protein. In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for arginosuccinate lyase protein. In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for arginase protein. 
     In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for a protein associated with a lysosomal storage disorder. In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for alpha galactosidase protein. In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for glucocerebrosidase protein. In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for iduronate-2-sulfatase protein. In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for iduronidase protein. In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for N-acetyl-alpha-D-glucosaminidase protein. In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for heparan N-sulfatase protein. In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for galactosamine-6 sulfatase protein. In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for beta-galactosidase protein. In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for lysosomal lipase protein. In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for arylsulfatase B (N-acetylgalactosamine-4-sulfatase) protein. In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for transcription factor EB (TFEB). 
     in certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for a protein associated with a glycogen storage disorder. In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for acid alpha-glucosidase protein. In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for glucose-6-phosphatase (GGPC) protein. In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for liver glycogen phosphorylase protein. In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for muscle phosphoglycerate mutase protein. In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for glycogen debranching enzyme. 
     In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for a protein associated with amino acid metabolism. In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for phenylalanine hydroxylase enzyme. In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for glutaryl-CoA dehydrogenase enzyme. In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for propionyl-CoA caboxylase enzyme. In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for oxalase alanine-glyoxylate aminotransferase enzyme. 
     In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for a protein associated with a lipid metabolism or fibrotic disorder. In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for a mTOR inhibitor. In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for ATPase phospholipid transporting 8B1 (ATP8B1) protein. In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for one or more NF-kappa B inhibitors, such as one or more of I-kappa B alpha, interferon-related development regulator 1 (IFRD1), and Sirtuin 1 (SIRT1). In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for PPAR-gamma protein or an active variant. 
     In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for a protein associated with methylmalonic acidemia. For example, in certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for methylmalonyl CoA mutase protein. In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for methylmalonyl CoA epimerase protein. 
     In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA for which delivery to or treatment of the liver can provide therapeutic benefit. In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for ATP7B protein, also known as Wilson disease protein. In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for porphobilinogen deaminase enzyme. In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for one or clotting enzymes, such as Factor VII, Factor IX, Factor VH, and Factor X. In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for human hemochromatosis (HFE) protein. 
     In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes a peptide or protein for use in the delivery to or treatment of the cardiovasculature of a subject or a cardiovascular cell. In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for vascular endothelial growth factor A protein. In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for relaxin protein. In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for bone morphogenetic protein-9 protein. In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for bone morphogenetic protein-2 receptor protein. 
     In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes a peptide or protein for use in the delivery to or treatment of the muscle of a subject or a muscle cell. In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for dystrophin protein. In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for frataxin protein. In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes a peptide or protein for use in the delivery to or treatment of the cardiac muscle of a subject or a cardiac muscle cell. In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for a protein that modulates one or both of a potassium channel and a sodium channel in muscle tissue or in a muscle cell. In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for a protein that modulates a Kv7.1 channel in muscle tissue or in a muscle cell. In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for a protein that modulates a Nav1.5 channel in muscle tissue or in a muscle cell. 
     In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes a peptide or protein for use in the delivery to or treatment of the nervous system of a subject or a nervous system cell. For example, in certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for survival motor neuron 1 protein. For example, in certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for survival motor neuron 2 protein. In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for frataxin protein. In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for ATP binding cassette subfamily D member 1 (ABCD1) protein. In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for CLN3 protein. 
     In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes a peptide or protein for use in the delivery to or treatment of the blood or bone marrow of a subject or a blood or bone marrow cell. In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for beta globin protein. In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for Bruton&#39;s tyrosine kinase protein. In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for one or clotting enzymes, such as Factor VIII, Factor IX, Factor VII, and Factor X. 
     In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes a peptide or protein for use in the delivery to or treatment of the kidney of a subject or a kidney cell. In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for collagen type IV alpha 5 chain (COL4A5) protein, 
     In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes a peptide or protein for use in the delivery to or treatment of the eye of a subject or an eye cell. In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for ATP-binding cassette sub-family A member 4 (ABCA4) protein. In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for retinoschisin protein. In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for retinal pigment epithelium-specific 65 kDa (RPE65) protein. In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for centrosomal protein of 290 kDa (CEP290). 
     In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes a peptide or protein for use in the delivery of or treatment with a vaccine for a subject or a cell of a subject. For example, in certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for an antigen from an infectious agent, such as a virus. In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for an antigen from influenza virus. In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for an antigen from respiratory syncytial virus. In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for an antigen from rabies virus. In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for an antigen from cytomegalovirus. In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for an antigen from rotavirus. In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for an antigen from a hepatitis virus, such as hepatitis A virus, hepatitis B virus, or hepatis C virus. In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for an antigen from human papillomavirus. In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for an antigen from a herpes simplex virus, such as herpes simplex virus 1 or herpes simplex virus 2. In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for an antigen from a human immunodeficiency virus, such as human immunodeficiency virus type 1 or human immunodeficiency virus type 2. In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for an antigen from a human metapneumovirus. In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for an antigen from a human parainfluenza virus, such as human parainfluenza virus type 1, human parainfluenza virus type 2, or human parainfluenza virus type 3. In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for an antigen from malaria virus. In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for an antigen from zika virus. In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for an antigen from chikungunya virus. 
     In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for an antigen associated with a cancer of a subject or identified from a cancer cell of a subject. In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for an antigen determined from a subject&#39;s own cancer cell, i.e., to provide a personalized cancer vaccine. In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for an antigen expressed from a mutant KRAS gene. 
     n certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for an antibody. In certain embodiments, the antibody can be a bi-specific antibody. In certain embodiments, the antibody can be part of a fusion protein. In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for an antibody to OX40. In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for an antibody to VEGF. In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for an antibody to tissue necrosis factor alpha. In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for an antibody to CD3. In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for an antibody to CD19. 
     In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for an immunomodulator. In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for Interleukin 12. In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for interleukin 23. In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for Interleukin 36 gamma. In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for a constitutively active variant of one or more stimulator of interferon genes (STING) proteins. 
     In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for an endonuclease. In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for an RNA-guided DNA endonuclease protein, such as Cas 9 protein. In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for a meganuclease protein. In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for a transcription activator-like effector nuclease protein. In certain embodiments the present invention provides a method for producing a therapeutic composition having full-length mRNA that encodes for a zinc finger nuclease protein. 
     In embodiments, exemplary therapeutic uses result from the delivery of mRNA encoding a secreted protein. Accordingly, in embodiments, the compositions and methods of the invention provide for delivery of mRNA encoding a secreted protein. In some embodiments, the compositions and methods of the invention provide for delivery of mRNA encoding one or more secreted proteins listed in Table 1; thus, compositions of the invention may comprise an mRNA encoding a protein listed in Table 1 (or a homolog thereof) along with other components set out herein, and methods of the invention may comprise preparing and/or administering a composition comprising an mRNA encoding a protein listed in Table 1 (or a homolog thereof) along with other components set out herein. 
     
       
         
           
               
             
               
                 TABLE 1 
               
             
            
               
                   
               
               
                 Secreted Proteins 
               
            
           
           
               
               
               
            
               
                 Uniprot ID 
                 Protein Name 
                 Gene Name 
               
               
                   
               
               
                 A1E959 
                 Odontogenic ameloblast-associated protein 
                 ODAM 
               
               
                 A1KZ92 
                 Peroxidasin-like protein 
                 PXDNL 
               
               
                 A1L453 
                 Serine protease 38 
                 PRSS38 
               
               
                 A1L4H1 
                 Soluble scavenger receptor cysteine-rich domain- 
                 SSC5D 
               
               
                   
                 containing protein SSC5D 
               
               
                 A2RUU4 
                 Colipase-like protein 1 
                 CLPSL1 
               
               
                 A2VDF0 
                 Fucose mutarotase 
                 FUOM 
               
               
                 A2VEC9 
                 SCO-spondin 
                 SSPO 
               
               
                 A3KMH1 
                 von Willebrand factor A domain-containing 
                 VWA8 
               
               
                   
                 protein 8 
               
               
                 A4D0S4 
                 Laminin subunit beta-4 
                 LAMB4 
               
               
                 A4D1T9 
                 Probable inactive serine protease 37 
                 PRSS37 
               
               
                 A5D8T8 
                 C-type lectin domain family 18 member A 
                 CLEC18A 
               
               
                 A6NC86 
                 phospholipase A2 inhibitor and Ly6/PLAUR 
                 PINLYP 
               
               
                   
                 domain-containing protein 
               
               
                 A6NCI4 
                 von Willebrand factor A domain-containing 
                 VWA3A 
               
               
                   
                 protein 3A 
               
               
                 A6ND01 
                 Probable folate receptor delta 
                 FOLR4 
               
               
                 A6NDD2 
                 Beta-defensin 108B-like 
               
               
                 A6NE02 
                 BTB/POZ domain-containing protein 17 
                 BTBD17 
               
               
                 A6NEF6 
                 Growth hormone 1 
                 GH1 
               
               
                 A6NF02 
                 NPIP-like protein LOC730153 
               
               
                 A6NFB4 
                 HCG1749481, isoform CRA_k 
                 CSH1 
               
               
                 A6NFZ4 
                 Protein FAM24A 
                 FAM24A 
               
               
                 A6NG13 
                 Glycosyltransferase 54 domain-containing protein 
               
               
                 A6NGN9 
                 IgLON family member 5 
                 IGLON5 
               
               
                 A6NHN0 
                 Otolin-1 
                 OTOL1 
               
               
                 A6NHN6 
                 Nuclear pore complex-interacting protein-like 2 
                 NPIPL2 
               
               
                 A6NI73 
                 Leukocyte immunoglobulin-like receptor 
                 LILRA5 
               
               
                   
                 subfamily A member 5 
               
               
                 A6NIT4 
                 Chorionic somatomammotropin hormone 2 
                 CSH2 
               
               
                   
                 isoform 2 
               
               
                 A6NJ69 
                 IgA-inducing protein homolog 
                 IGIP 
               
               
                 A6NKQ9 
                 Choriogonadotropin subunit beta variant 1 
                 CGB1 
               
               
                 A6NMZ7 
                 Collagen alpha-6(VI) chain 
                 COL6A6 
               
               
                 A6NNS2 
                 Dehydrogenase/reductase SDR family member 7C 
                 DHRS7C 
               
               
                 A6XGL2 
                 Insulin A chain 
                 INS 
               
               
                 A8K0G1 
                 Protein Wnt 
                 WNT7B 
               
               
                 A8K2U0 
                 Alpha-2-macroglobulin-like protein 1 
                 A2ML1 
               
               
                 A8K7I4 
                 Calcium-activated chloride channel regulator 1 
                 CLCA1 
               
               
                 A8MTL9 
                 Serpin-like protein HMSD 
                 HMSD 
               
               
                 A8MV23 
                 Serpin E3 
                 SERPINE3 
               
               
                 A8MZH6 
                 Oocyte-secreted protein 1 homolog 
                 OOSP1 
               
               
                 A8TX70 
                 Collagen alpha-5(VI) chain 
                 COL6A5 
               
               
                 B0ZBE8 
                 Natriuretic peptide 
                 NPPA 
               
               
                 B1A4G9 
                 Somatotropin 
                 GH1 
               
               
                 B1A4H2 
                 HCG1749481, isoform CRA_d 
                 CSH1 
               
               
                 B1A4H9 
                 Chorionic somatomammotropin hormone 
                 CSH2 
               
               
                 B1AJZ6 
                 Protein Wnt 
                 WNT4 
               
               
                 B1AKI9 
                 Isthmin-1 
                 ISM1 
               
               
                 B2RNN3 
                 Complement C1q and tumor necrosis factor- 
                 C1QTNF9B 
               
               
                   
                 related protein 9B 
               
               
                 B2RUY7 
                 von Willebrand factor C domain-containing 
                 VWC2L 
               
               
                   
                 protein 2-like 
               
               
                 B3GLJ2 
                 Prostate and testis expressed protein 3 
                 PATE3 
               
               
                 B4DI03 
                 SEC11-like 3 ( S. cerevisiae ), isoform CRA_a 
                 SEC11L3 
               
               
                 B4DJF9 
                 Protein Wnt 
                 WNT4 
               
               
                 B4DUL4 
                 SEC11-like 1 ( S. cerevisiae ), isoform CRA_d 
                 SEC11L1 
               
               
                 B5MCC8 
                 Protein Wnt 
                 WNT10B 
               
               
                 B8A595 
                 Protein Wnt 
                 WNT7B 
               
               
                 B8A597 
                 Protein Wnt 
                 WNT7B 
               
               
                 B8A598 
                 Protein Wnt 
                 WNT7B 
               
               
                 B9A064 
                 Immunoglobulin lambda-like polypeptide 5 
                 IGLL5 
               
               
                 C9J3H3 
                 Protein Wnt 
                 WNT10B 
               
               
                 C9J8I8 
                 Protein Wnt 
                 WNT5A 
               
               
                 C9JAF2 
                 Insulin-like growth factor II Ala-25 Del 
                 IGF2 
               
               
                 C9JCI2 
                 Protein Wnt 
                 WNT10B 
               
               
                 C9JL84 
                 HERV-H LTR-associating protein 1 
                 HHLA1 
               
               
                 C9JNR5 
                 Insulin A chain 
                 INS 
               
               
                 C9JUI2 
                 Protein Wnt 
                 WNT2 
               
               
                 D6RF47 
                 Protein Wnt 
                 WNT8A 
               
               
                 D6RF94 
                 Protein Wnt 
                 WNT8A 
               
               
                 E2RYF7 
                 Protein PBMUCL2 
                 HCG22 
               
               
                 E5RFR1 
                 PENK(114-133) 
                 PENK 
               
               
                 E7EML9 
                 Serine protease 44 
                 PRSS44 
               
               
                 E7EPC3 
                 Protein Wnt 
                 WNT9B 
               
               
                 E7EVP0 
                 Nociceptin 
                 PNOC 
               
               
                 E9PD02 
                 Insulin-like growth factor I 
                 IGF1 
               
               
                 E9PH60 
                 Protein Wnt 
                 WNT16 
               
               
                 E9PJL6 
                 Protein Wnt 
                 WNT11 
               
               
                 F5GYM2 
                 Protein Wnt 
                 WNT5B 
               
               
                 F5H034 
                 Protein Wnt 
                 WNT5B 
               
               
                 F5H364 
                 Protein Wnt 
                 WNT5B 
               
               
                 F5H7Q6 
                 Protein Wnt 
                 WNT5B 
               
               
                 F8WCM5 
                 Protein INS-IGF2 
                 INS-IGF2 
               
               
                 F8WDR1 
                 Protein Wnt 
                 WNT2 
               
               
                 H0Y663 
                 Protein Wnt 
                 WNT4 
               
               
                 H0YK72 
                 Signal peptidase complex catalytic subunit 
                 SEC11A 
               
               
                   
                 SEC11A 
               
               
                 H0YK83 
                 Signal peptidase complex catalytic subunit 
                 SEC11A 
               
               
                   
                 SEC11A 
               
               
                 H0YM39 
                 Chorionic somatomammotropin hormone 
                 CSH2 
               
               
                 H0YMT7 
                 Chorionic somatomammotropin hormone 
                 CSH1 
               
               
                 H0YN17 
                 Chorionic somatomammotropin hormone 
                 CSH2 
               
               
                 H0YNA5 
                 Signal peptidase complex catalytic subunit 
                 SEC11A 
               
               
                   
                 SEC11A 
               
               
                 H0YNG3 
                 Signal peptidase complex catalytic subunit 
                 SEC11A 
               
               
                   
                 SEC11A 
               
               
                 H0YNX5 
                 Signal peptidase complex catalytic subunit 
                 SEC11A 
               
               
                   
                 SEC11A 
               
               
                 H7BZB8 
                 Protein Wnt 
                 WNT10A 
               
               
                 H9KV56 
                 Choriogonadotropin subunit beta variant 2 
                 CGB2 
               
               
                 I3L0L8 
                 Protein Wnt 
                 WNT9B 
               
               
                 J3KNZ1 
                 Choriogonadotropin subunit beta variant 1 
                 CGB1 
               
               
                 J3KP00 
                 Choriogonadotropin subunit beta 
                 CGB7 
               
               
                 J3QT02 
                 Choriogonadotropin subunit beta variant 1 
                 CGB1 
               
               
                 O00175 
                 C-C motif chemokine 24 
                 CCL24 
               
               
                 O00182 
                 Galectin-9 
                 LGALS9 
               
               
                 O00187 
                 Mannan-binding lectin serine protease 2 
                 MASP2 
               
               
                 O00230 
                 Cortistatin 
                 CORT 
               
               
                 O00253 
                 Agouti-related protein 
                 AGRP 
               
               
                 O00270 
                 12-(S)-hydroxy-5,8,10,14-eicosatetraenoic acid 
                 GPR31 
               
               
                   
                 receptor 
               
               
                 O00292 
                 Left-right determination factor 2 
                 LEFTY2 
               
               
                 O00294 
                 Tubby-related protein 1 
                 TULP1 
               
               
                 O00295 
                 Tubby-related protein 2 
                 TULP2 
               
               
                 O00300 
                 Tumor necrosis factor receptor superfamily 
                 TNFRSF11B 
               
               
                   
                 member 11B 
               
               
                 O00339 
                 Matrilin-2 
                 MATN2 
               
               
                 O00391 
                 Sulfhydryl oxidase 1 
                 QSOX1 
               
               
                 O00468 
                 Agrin 
                 AGRN 
               
               
                 O00515 
                 Ladinin-1 
                 LAD1 
               
               
                 O00533 
                 Processed neural cell adhesion molecule L1-like 
                 CHL1 
               
               
                   
                 protein 
               
               
                 O00584 
                 Ribonuclease T2 
                 RNASET2 
               
               
                 O00585 
                 C-C motif chemokine 21 
                 CCL21 
               
               
                 O00602 
                 Ficolin-1 
                 FCN1 
               
               
                 O00622 
                 Protein CYR61 
                 CYR61 
               
               
                 O00626 
                 MDC(5-69) 
                 CCL22 
               
               
                 O00634 
                 Netrin-3 
                 NTN3 
               
               
                 O00744 
                 Protein Wnt-10b 
                 WNT10B 
               
               
                 O00755 
                 Protein Wnt-7a 
                 WNT7A 
               
               
                 O14498 
                 Immunoglobulin superfamily containing leucine- 
                 ISLR 
               
               
                   
                 rich repeat protein 
               
               
                 O14511 
                 Pro-neuregulin-2, membrane-bound isoform 
                 NRG2 
               
               
                 O14594 
                 Neurocan core protein 
                 NCAN 
               
               
                 O14625 
                 C-X-C motif chemokine 11 
                 CXCL11 
               
               
                 O14638 
                 Ectonucleotide 
                 ENPP3 
               
               
                   
                 pyrophosphatase/phosphodiesterase family 
               
               
                   
                 member 3 
               
               
                 O14656 
                 Torsin-1A 
                 TOR1A 
               
               
                 O14657 
                 Torsin-1B 
                 TOR1B 
               
               
                 O14786 
                 Neuropilin-1 
                 NRP1 
               
               
                 O14788 
                 Tumor necrosis factor ligand superfamily member 
                 TNFSF11 
               
               
                   
                 11, membrane form 
               
               
                 O14791 
                 Apolipoprotein L1 
                 APOL1 
               
               
                 O14793 
                 Growth/differentiation factor 8 
                 MSTN 
               
               
                 O14904 
                 Protein Wnt-9a 
                 WNT9A 
               
               
                 O14905 
                 Protein Wnt-9b 
                 WNT9B 
               
               
                 O14944 
                 Proepiregulin 
                 EREG 
               
               
                 O14960 
                 Leukocyte cell-derived chemotaxin-2 
                 LECT2 
               
               
                 O15018 
                 Processed PDZ domain-containing protein 2 
                 PDZD2 
               
               
                 O15041 
                 Semaphorin-3E 
                 SEMA3E 
               
               
                 O15072 
                 A disintegrin and metalloproteinase with 
                 ADAMTS3 
               
               
                   
                 thrombospondin motifs 3 
               
               
                 O15123 
                 Angiopoietin-2 
                 ANGPT2 
               
               
                 O15130 
                 Neuropeptide FF 
                 NPFF 
               
               
                 O15197 
                 Ephrin type-B receptor 6 
                 EPHB6 
               
               
                 O15204 
                 ADAM DEC1 
                 ADAMDEC1 
               
               
                 O15230 
                 Laminin subunit alpha-5 
                 LAMA5 
               
               
                 O15232 
                 Matrilin-3 
                 MATN3 
               
               
                 O15240 
                 Neuroendocrine regulatory peptide-1 
                 VGF 
               
               
                 O15263 
                 Beta-defensin 4A 
                 DEFB4A 
               
               
                 O15335 
                 Chondroadherin 
                 CHAD 
               
               
                 O15393 
                 Transmembrane protease serine 2 catalytic chain 
                 TMPRSS2 
               
               
                 O15444 
                 C-C motif chemokine 25 
                 CCL25 
               
               
                 O15467 
                 C-C motif chemokine 16 
                 CCL16 
               
               
                 O15496 
                 Group 10 secretory phospholipase A2 
                 PLA2G10 
               
               
                 O15520 
                 Fibroblast growth factor 10 
                 FGF10 
               
               
                 O15537 
                 Retinoschisin 
                 RS1 
               
               
                 O43157 
                 Plexin-B1 
                 PLXNB1 
               
               
                 O43184 
                 Disintegrin and metalloproteinase domain- 
                 ADAM12 
               
               
                   
                 containing protein 12 
               
               
                 O43240 
                 Kallikrein-10 
                 KLK10 
               
               
                 O43278 
                 Kunitz-type protease inhibitor 1 
                 SPINT1 
               
               
                 O43320 
                 Fibroblast growth factor 16 
                 FGF16 
               
               
                 O43323 
                 Desert hedgehog protein C-product 
                 DHH 
               
               
                 O43405 
                 Cochlin 
                 COCH 
               
               
                 O43508 
                 Tumor necrosis factor ligand superfamily member 
                 TNFSF12 
               
               
                   
                 12, membrane form 
               
               
                 O43555 
                 Progonadoliberin-2 
                 GNRH2 
               
               
                 O43557 
                 Tumor necrosis factor ligand superfamily member 
                 TNFSF14 
               
               
                   
                 14, soluble form 
               
               
                 O43692 
                 Peptidase inhibitor 15 
                 PI15 
               
               
                 O43699 
                 Sialic acid-binding Ig-like lectin 6 
                 SIGLEC6 
               
               
                 O43820 
                 Hyaluronidase-3 
                 HYAL3 
               
               
                 O43827 
                 Angiopoietin-related protein 7 
                 ANGPTL7 
               
               
                 O43852 
                 Calumenin 
                 CALU 
               
               
                 O43854 
                 EGF-like repeat and discoidin I-like domain- 
                 EDIL3 
               
               
                   
                 containing protein 3 
               
               
                 O43866 
                 CD5 antigen-like 
                 CD5L 
               
               
                 O43897 
                 Tolloid-like protein 1 
                 TLL1 
               
               
                 O43915 
                 Vascular endothelial growth factor D 
                 FIGF 
               
               
                 O43927 
                 C-X-C motif chemokine 13 
                 CXCL13 
               
               
                 O60218 
                 Aldo-keto reductase family 1 member B10 
                 AKR1B10 
               
               
                 O60235 
                 Transmembrane protease serine 11D 
                 TMPRSS11D 
               
               
                 O60258 
                 Fibroblast growth factor 17 
                 FGF17 
               
               
                 O60259 
                 Kallikrein-8 
                 KLK8 
               
               
                 O60383 
                 Growth/differentiation factor 9 
                 GDF9 
               
               
                 O60469 
                 Down syndrome cell adhesion molecule 
                 DSCAM 
               
               
                 O60542 
                 Persephin 
                 PSPN 
               
               
                 O60565 
                 Gremlin-1 
                 GREM1 
               
               
                 O60575 
                 Serine protease inhibitor Kazal-type 4 
                 SPINK4 
               
               
                 O60676 
                 Cystatin-8 
                 CST8 
               
               
                 O60687 
                 Sushi repeat-containing protein SRPX2 
                 SRPX2 
               
               
                 O60844 
                 Zymogen granule membrane protein 16 
                 ZG16 
               
               
                 O60882 
                 Matrix metalloproteinase-20 
                 MMP20 
               
               
                 O60938 
                 Keratocan 
                 KERA 
               
               
                 O75015 
                 Low affinity immunoglobulin gamma Fc region 
                 FCGR3B 
               
               
                   
                 receptor III-B 
               
               
                 O75077 
                 Disintegrin and metalloproteinase domain- 
                 ADAM23 
               
               
                   
                 containing protein 23 
               
               
                 O75093 
                 Slit homolog 1 protein 
                 SLIT1 
               
               
                 O75094 
                 Slit homolog 3 protein 
                 SLIT3 
               
               
                 O75095 
                 Multiple epidermal growth factor-like domains 
                 MEGF6 
               
               
                   
                 protein 6 
               
               
                 O75173 
                 A disintegrin and metalloproteinase with 
                 ADAMTS4 
               
               
                   
                 thrombospondin motifs 4 
               
               
                 O75200 
                 Nuclear pore complex-interacting protein-like 1 
                 NPIPL1 
               
               
                 O75339 
                 Cartilage intermediate layer protein 1 C1 
                 CILP 
               
               
                 O75354 
                 Ectonucleoside triphosphate diphosphohydrolase 6 
                 ENTPD6 
               
               
                 O75386 
                 Tubby-related protein 3 
                 TULP3 
               
               
                 O75398 
                 Deformed epidermal autoregulatory factor 1 
                 DEAF1 
               
               
                   
                 homolog 
               
               
                 O75443 
                 Alpha-tectorin 
                 TECTA 
               
               
                 O75445 
                 Usherin 
                 USH2A 
               
               
                 O75462 
                 Cytokine receptor-like factor 1 
                 CRLF1 
               
               
                 O75487 
                 Glypican-4 
                 GPC4 
               
               
                 O75493 
                 Carbonic anhydrase-related protein 11 
                 CA11 
               
               
                 O75594 
                 Peptidoglycan recognition protein 1 
                 PGLYRP1 
               
               
                 O75596 
                 C-type lectin domain family 3 member A 
                 CLEC3A 
               
               
                 O75610 
                 Left-right determination factor 1 
                 LEFTY1 
               
               
                 O75629 
                 Protein CREG1 
                 CREG1 
               
               
                 O75636 
                 Ficolin-3 
                 FCN3 
               
               
                 O75711 
                 Scrapie-responsive protein 1 
                 SCRG1 
               
               
                 O75715 
                 Epididymal secretory glutathione peroxidase 
                 GPX5 
               
               
                 O75718 
                 Cartilage-associated protein 
                 CRTAP 
               
               
                 O75829 
                 Chondrosurfactant protein 
                 LECT1 
               
               
                 O75830 
                 Serpin I2 
                 SERPINI2 
               
               
                 O75882 
                 Attractin 
                 ATRN 
               
               
                 O75888 
                 Tumor necrosis factor ligand superfamily member 
                 TNFSF13 
               
               
                   
                 13 
               
               
                 O75900 
                 Matrix metalloproteinase-23 
                 MMP23A 
               
               
                 O75951 
                 Lysozyme-like protein 6 
                 LYZL6 
               
               
                 O75973 
                 C1q-related factor 
                 C1QL1 
               
               
                 O76038 
                 Secretagogin 
                 SCGN 
               
               
                 O76061 
                 Stanniocalcin-2 
                 STC2 
               
               
                 O76076 
                 WNT1-inducible-signaling pathway protein 2 
                 WISP2 
               
               
                 O76093 
                 Fibroblast growth factor 18 
                 FGF18 
               
               
                 O76096 
                 Cystatin-F 
                 CST7 
               
               
                 O94769 
                 Extracellular matrix protein 2 
                 ECM2 
               
               
                 O94813 
                 Slit homolog 2 protein C-product 
                 SLIT2 
               
               
                 O94907 
                 Dickkopf-related protein 1 
                 DKK1 
               
               
                 O94919 
                 Endonuclease domain-containing 1 protein 
                 ENDOD1 
               
               
                 O94964 
                 N-terminal form 
                 SOGA1 
               
               
                 O95025 
                 Semaphorin-3D 
                 SEMA3D 
               
               
                 O95084 
                 Serine protease 23 
                 PRSS23 
               
               
                 O95150 
                 Tumor necrosis factor ligand superfamily member 
                 TNFSF15 
               
               
                   
                 15 
               
               
                 O95156 
                 Neurexophilin-2 
                 NXPH2 
               
               
                 O95157 
                 Neurexophilin-3 
                 NXPH3 
               
               
                 O95158 
                 Neurexophilin-4 
                 NXPH4 
               
               
                 O95388 
                 WNT1-inducible-signaling pathway protein 1 
                 WISP1 
               
               
                 O95389 
                 WNT1-inducible-signaling pathway protein 3 
                 WISP3 
               
               
                 O95390 
                 Growth/differentiation factor 11 
                 GDF11 
               
               
                 O95393 
                 Bone morphogenetic protein 10 
                 BMP10 
               
               
                 O95399 
                 Urotensin-2 
                 UTS2 
               
               
                 O95407 
                 Tumor necrosis factor receptor superfamily 
                 TNFRSF6B 
               
               
                   
                 member 6B 
               
               
                 O95428 
                 Papilin 
                 PAPLN 
               
               
                 O95445 
                 Apolipoprotein M 
                 APOM 
               
               
                 O95450 
                 A disintegrin and metalloproteinase with 
                 ADAMTS2 
               
               
                   
                 thrombospondin motifs 2 
               
               
                 O95460 
                 Matrilin-4 
                 MATN4 
               
               
                 O95467 
                 LHAL tetrapeptide 
                 GNAS 
               
               
                 O95631 
                 Netrin-1 
                 NTN1 
               
               
                 O95633 
                 Follistatin-related protein 3 
                 FSTL3 
               
               
                 O95711 
                 Lymphocyte antigen 86 
                 LY86 
               
               
                 O95715 
                 C-X-C motif chemokine 14 
                 CXCL14 
               
               
                 O95750 
                 Fibroblast growth factor 19 
                 FGF19 
               
               
                 O95760 
                 Interleukin-33 
                 IL33 
               
               
                 O95813 
                 Cerberus 
                 CER1 
               
               
                 O95841 
                 Angiopoietin-related protein 1 
                 ANGPTL1 
               
               
                 O95897 
                 Noelin-2 
                 OLFM2 
               
               
                 O95925 
                 Eppin 
                 EPPIN 
               
               
                 O95965 
                 Integrin beta-like protein 1 
                 ITGBL1 
               
               
                 O95967 
                 EGF-containing fibulin-like extracellular matrix 
                 EFEMP2 
               
               
                   
                 protein 2 
               
               
                 O95968 
                 Secretoglobin family 1D member 1 
                 SCGB1D1 
               
               
                 O95969 
                 Secretoglobin family 1D member 2 
                 SCGB1D2 
               
               
                 O95970 
                 Leucine-rich glioma-inactivated protein 1 
                 LGI1 
               
               
                 O95972 
                 Bone morphogenetic protein 15 
                 BMP15 
               
               
                 O95994 
                 Anterior gradient protein 2 homolog 
                 AGR2 
               
               
                 O95998 
                 Interleukin-18-binding protein 
                 IL18BP 
               
               
                 O96009 
                 Napsin-A 
                 NAPSA 
               
               
                 O96014 
                 Protein Wnt-11 
                 WNT11 
               
               
                 P00450 
                 Ceruloplasmin 
                 CP 
               
               
                 P00451 
                 Factor VIIIa light chain 
                 F8 
               
               
                 P00488 
                 Coagulation factor XIII A chain 
                 F13A1 
               
               
                 P00533 
                 Epidermal growth factor receptor 
                 EGFR 
               
               
                 P00709 
                 Alpha-lactalbumin 
                 LALBA 
               
               
                 P00734 
                 Prothrombin 
                 F2 
               
               
                 P00738 
                 Haptoglobin beta chain 
                 HP 
               
               
                 P00739 
                 Haptoglobin-related protein 
                 HPR 
               
               
                 P00740 
                 Coagulation factor IXa heavy chain 
                 F9 
               
               
                 P00742 
                 Factor X heavy chain 
                 F10 
               
               
                 P00746 
                 Complement factor D 
                 CFD 
               
               
                 P00747 
                 Plasmin light chain B 
                 PLG 
               
               
                 P00748 
                 Coagulation factor XIIa light chain 
                 F12 
               
               
                 P00749 
                 Urokinase-type plasminogen activator long 
                 PLAU 
               
               
                   
                 chain A 
               
               
                 P00750 
                 Tissue-type plasminogen activator 
                 PLAT 
               
               
                 P00751 
                 Complement factor B Ba fragment 
                 CFB 
               
               
                 P00797 
                 Renin 
                 REN 
               
               
                 P00973 
                 2′-5′-oligoadenylate synthase 1 
                 OAS1 
               
               
                 P00995 
                 Pancreatic secretory trypsin inhibitor 
                 SPINK1 
               
               
                 P01008 
                 Antithrombin-III 
                 SERPINC1 
               
               
                 P01009 
                 Alpha-1-antitrypsin 
                 SERPINA1 
               
               
                 P01011 
                 Alpha-1-antichymotrypsin His-Pro-less 
                 SERPINA3 
               
               
                 P01019 
                 Angiotensin-1 
                 AGT 
               
               
                 P01023 
                 Alpha-2-macroglobulin 
                 A2M 
               
               
                 P01024 
                 Acylation stimulating protein 
                 C3 
               
               
                 P01031 
                 Complement C5 beta chain 
                 C5 
               
               
                 P01033 
                 Metalloproteinase inhibitor 1 
                 TIMP1 
               
               
                 P01034 
                 Cystatin-C 
                 CST3 
               
               
                 P01036 
                 Cystatin-S 
                 CST4 
               
               
                 P01037 
                 Cystatin-SN 
                 CST1 
               
               
                 P01042 
                 Kininogen-1 light chain 
                 KNG1 
               
               
                 P01127 
                 Platelet-derived growth factor subunit B 
                 PDGFB 
               
               
                 P01135 
                 Transforming growth factor alpha 
                 TGFA 
               
               
                 P01137 
                 Transforming growth factor beta-1 
                 TGFB1 
               
               
                 P01138 
                 Beta-nerve growth factor 
                 NGF 
               
               
                 P01148 
                 Gonadoliberin-1 
                 GNRH1 
               
               
                 P01160 
                 Atrial natriuretic factor 
                 NPPA 
               
               
                 P01178 
                 Oxytocin 
                 OXT 
               
               
                 P01185 
                 Vasopressin-neurophysin 2-copeptin 
                 AVP 
               
               
                 P01189 
                 Corticotropin 
                 POMC 
               
               
                 P01210 
                 PENK(237-258) 
                 PENK 
               
               
                 P01213 
                 Alpha-neoendorphin 
                 PDYN 
               
               
                 P01215 
                 Glycoprotein hormones alpha chain 
                 CGA 
               
               
                 P01222 
                 Thyrotropin subunit beta 
                 TSHB 
               
               
                 P01225 
                 Follitropin subunit beta 
                 FSHB 
               
               
                 P01229 
                 Lutropin subunit beta 
                 LHB 
               
               
                 P01233 
                 Choriogonadotropin subunit beta 
                 CGB8 
               
               
                 P01236 
                 Prolactin 
                 PRL 
               
               
                 P01241 
                 Somatotropin 
                 GH1 
               
               
                 P01242 
                 Growth hormone variant 
                 GH2 
               
               
                 P01243 
                 Chorionic somatomammotropin hormone 
                 CSH2 
               
               
                 P01258 
                 Katacalcin 
                 CALCA 
               
               
                 P01266 
                 Thyroglobulin 
                 TG 
               
               
                 P01270 
                 Parathyroid hormone 
                 PTH 
               
               
                 P01275 
                 Glucagon 
                 GCG 
               
               
                 P01282 
                 Intestinal peptide PHM-27 
                 VIP 
               
               
                 P01286 
                 Somatoliberin 
                 GHRH 
               
               
                 P01298 
                 Pancreatic prohormone 
                 PPY 
               
               
                 P01303 
                 C-flanking peptide of NPY 
                 NPY 
               
               
                 P01308 
                 Insulin 
                 INS 
               
               
                 P01344 
                 Insulin-like growth factor II 
                 IGF2 
               
               
                 P01350 
                 Big gastrin 
                 GAST 
               
               
                 P01374 
                 Lymphotoxin-alpha 
                 LTA 
               
               
                 P01375 
                 C-domain 1 
                 TNF 
               
               
                 P01562 
                 Interferon alpha-1/13 
                 IFNA1 
               
               
                 P01563 
                 Interferon alpha-2 
                 IFNA2 
               
               
                 P01566 
                 Interferon alpha-10 
                 IFNA10 
               
               
                 P01567 
                 Interferon alpha-7 
                 IFNA7 
               
               
                 P01568 
                 Interferon alpha-21 
                 IFNA21 
               
               
                 P01569 
                 Interferon alpha-5 
                 IFNA5 
               
               
                 P01570 
                 Interferon alpha-14 
                 IFNA14 
               
               
                 P01571 
                 Interferon alpha-17 
                 IFNA17 
               
               
                 P01574 
                 Interferon beta 
                 IFNB1 
               
               
                 P01579 
                 Interferon gamma 
                 IFNG 
               
               
                 P01583 
                 Interleukin-1 alpha 
                 IL1A 
               
               
                 P01584 
                 Interleukin-1 beta 
                 IL1B 
               
               
                 P01588 
                 Erythropoietin 
                 EPO 
               
               
                 P01591 
                 Immunoglobulin J chain 
                 IGJ 
               
               
                 P01732 
                 T-cell surface glycoprotein CD8 alpha chain 
                 CD8A 
               
               
                 P01833 
                 Polymeric immunoglobulin receptor 
                 PIGR 
               
               
                 P01857 
                 Ig gamma-1 chain C region 
                 IGHG1 
               
               
                 P01859 
                 Ig gamma-2 chain C region 
                 IGHG2 
               
               
                 P01860 
                 Ig gamma-3 chain C region 
                 IGHG3 
               
               
                 P01861 
                 Ig gamma-4 chain C region 
                 IGHG4 
               
               
                 P01871 
                 Ig mu chain C region 
                 IGHM 
               
               
                 P01880 
                 Ig delta chain C region 
                 IGHD 
               
               
                 P02452 
                 Collagen alpha-1(I) chain 
                 COL1A1 
               
               
                 P02458 
                 Chondrocalcin 
                 COL2A1 
               
               
                 P02461 
                 Collagen alpha-1(III) chain 
                 COL3A1 
               
               
                 P02462 
                 Collagen alpha-1(IV) chain 
                 COL4A1 
               
               
                 P02647 
                 Apolipoprotein A-I 
                 APOA1 
               
               
                 P02649 
                 Apolipoprotein E 
                 APOE 
               
               
                 P02652 
                 Apolipoprotein A-II 
                 APOA2 
               
               
                 P02654 
                 Apolipoprotein C-I 
                 APOC1 
               
               
                 P02655 
                 Apolipoprotein C-II 
                 APOC2 
               
               
                 P02656 
                 Apolipoprotein C-III 
                 APOC3 
               
               
                 P02671 
                 Fibrinogen alpha chain 
                 FGA 
               
               
                 P02675 
                 Fibrinopeptide B 
                 FGB 
               
               
                 P02679 
                 Fibrinogen gamma chain 
                 FGG 
               
               
                 P02741 
                 C-reactive protein 
                 CRP 
               
               
                 P02743 
                 Serum amyloid P-component(1-203) 
                 APCS 
               
               
                 P02745 
                 Complement C1q subcomponent subunit A 
                 C1QA 
               
               
                 P02746 
                 Complement C1q subcomponent subunit B 
                 C1QB 
               
               
                 P02747 
                 Complement C1q subcomponent subunit C 
                 C1QC 
               
               
                 P02748 
                 Complement component C9b 
                 C9 
               
               
                 P02749 
                 Beta-2-glycoprotein 1 
                 APOH 
               
               
                 P02750 
                 Leucine-rich alpha-2-glycoprotein 
                 LRG1 
               
               
                 P02751 
                 Ugl-Y2 
                 FN1 
               
               
                 P02753 
                 Retinol-binding protein 4 
                 RBP4 
               
               
                 P02760 
                 Trypstatin 
                 AMBP 
               
               
                 P02763 
                 Alpha-1-acid glycoprotein 1 
                 ORM1 
               
               
                 P02765 
                 Alpha-2-HS-glycoprotein chain A 
                 AHSG 
               
               
                 P02766 
                 Transthyretin 
                 TTR 
               
               
                 P02768 
                 Serum albumin 
                 ALB 
               
               
                 P02771 
                 Alpha-fetoprotein 
                 AFP 
               
               
                 P02774 
                 Vitamin D-binding protein 
                 GC 
               
               
                 P02775 
                 Connective tissue-activating peptide III 
                 PPBP 
               
               
                 P02776 
                 Platelet factor 4 
                 PF4 
               
               
                 P02778 
                 CXCL10(1-73) 
                 CXCL10 
               
               
                 P02786 
                 Transferrin receptor protein 1 
                 TFRC 
               
               
                 P02787 
                 Serotransferrin 
                 TF 
               
               
                 P02788 
                 Lactoferroxin-C 
                 LTF 
               
               
                 P02790 
                 Hemopexin 
                 HPX 
               
               
                 P02808 
                 Statherin 
                 STATH 
               
               
                 P02810 
                 Salivary acidic proline-rich phosphoprotein 1/2 
                 PRH2 
               
               
                 P02812 
                 Basic salivary proline-rich protein 2 
                 PRB2 
               
               
                 P02814 
                 Peptide D1A 
                 SMR3B 
               
               
                 P02818 
                 Osteocalcin 
                 BGLAP 
               
               
                 P03950 
                 Angiogenin 
                 ANG 
               
               
                 P03951 
                 Coagulation factor XIa heavy chain 
                 F11 
               
               
                 P03952 
                 Plasma kallikrein 
                 KLKB1 
               
               
                 P03956 
                 27 kDa interstitial collagenase 
                 MMP1 
               
               
                 P03971 
                 Muellerian-inhibiting factor 
                 AMH 
               
               
                 P03973 
                 Antileukoproteinase 
                 SLPI 
               
               
                 P04003 
                 C4b-binding protein alpha chain 
                 C4BPA 
               
               
                 P04004 
                 Somatomedin-B 
                 VTN 
               
               
                 P04054 
                 Phospholipase A2 
                 PLA2G1B 
               
               
                 P04085 
                 Platelet-derived growth factor subunit A 
                 PDGFA 
               
               
                 P04090 
                 Relaxin A chain 
                 RLN2 
               
               
                 P04114 
                 Apolipoprotein B-100 
                 APOB 
               
               
                 P04118 
                 Colipase 
                 CLPS 
               
               
                 P04141 
                 Granulocyte-macrophage colony-stimulating 
                 CSF2 
               
               
                   
                 factor 
               
               
                 P04155 
                 Trefoil factor 1 
                 TFF1 
               
               
                 P04180 
                 Phosphatidylcholine-sterol acyltransferase 
                 LCAT 
               
               
                 P04196 
                 Histidine-rich glycoprotein 
                 HRG 
               
               
                 P04217 
                 Alpha-1B-glycoprotein 
                 A1BG 
               
               
                 P04275 
                 von Willebrand antigen 2 
                 VWF 
               
               
                 P04278 
                 Sex hormone-binding globulin 
                 SHBG 
               
               
                 P04279 
                 Alpha-inhibin-31 
                 SEMG1 
               
               
                 P04280 
                 Basic salivary proline-rich protein 1 
                 PRB1 
               
               
                 P04628 
                 Proto-oncogene Wnt-1 
                 WNT1 
               
               
                 P04745 
                 Alpha-amylase 1 
                 AMY1A 
               
               
                 P04746 
                 Pancreatic alpha-amylase 
                 AMY2A 
               
               
                 P04808 
                 Prorelaxin H1 
                 RLN1 
               
               
                 P05000 
                 Interferon omega-1 
                 IFNW1 
               
               
                 P05013 
                 Interferon alpha-6 
                 IFNA6 
               
               
                 P05014 
                 Interferon alpha-4 
                 IFNA4 
               
               
                 P05015 
                 Interferon alpha-16 
                 IFNA16 
               
               
                 P05019 
                 Insulin-like growth factor I 
                 IGF1 
               
               
                 P05060 
                 GAWK peptide 
                 CHGB 
               
               
                 P05090 
                 Apolipoprotein D 
                 APOD 
               
               
                 P05109 
                 Protein S100-A8 
                 S100A8 
               
               
                 P05111 
                 Inhibin alpha chain 
                 INHA 
               
               
                 P05112 
                 Interleukin-4 
                 IL4 
               
               
                 P05113 
                 Interleukin-5 
                 IL5 
               
               
                 P05120 
                 Plasminogen activator inhibitor 2 
                 SERPINB2 
               
               
                 P05121 
                 Plasminogen activator inhibitor 1 
                 SERPINE1 
               
               
                 P05154 
                 Plasma serine protease inhibitor 
                 SERPINA5 
               
               
                 P05155 
                 Plasma protease C1 inhibitor 
                 SERPING1 
               
               
                 P05156 
                 Complement factor I heavy chain 
                 CFI 
               
               
                 P05160 
                 Coagulation factor XIII B chain 
                 F13B 
               
               
                 P05161 
                 Ubiquitin-like protein ISG15 
                 ISG15 
               
               
                 P05230 
                 Fibroblast growth factor 1 
                 FGF1 
               
               
                 P05231 
                 Interleukin-6 
                 IL6 
               
               
                 P05305 
                 Big endothelin-1 
                 EDN1 
               
               
                 P05408 
                 C-terminal peptide 
                 SCG5 
               
               
                 P05451 
                 Lithostathine-1-alpha 
                 REG1A 
               
               
                 P05452 
                 Tetranectin 
                 CLEC3B 
               
               
                 P05543 
                 Thyroxine-binding globulin 
                 SERPINA7 
               
               
                 P05814 
                 Beta-casein 
                 CSN2 
               
               
                 P05997 
                 Collagen alpha-2(V) chain 
                 COL5A2 
               
               
                 P06276 
                 Cholinesterase 
                 BCHE 
               
               
                 P06307 
                 Cholecystokinin-12 
                 CCK 
               
               
                 P06396 
                 Gelsolin 
                 GSN 
               
               
                 P06681 
                 Complement C2 
                 C2 
               
               
                 P06702 
                 Protein S100-A9 
                 S100A9 
               
               
                 P06727 
                 Apolipoprotein A-IV 
                 APOA4 
               
               
                 P06734 
                 Low affinity immunoglobulin epsilon Fc receptor 
                 FCER2 
               
               
                   
                 soluble form 
               
               
                 P06744 
                 Glucose-6-phosphate isomerase 
                 GPI 
               
               
                 P06850 
                 Corticoliberin 
                 CRH 
               
               
                 P06858 
                 Lipoprotein lipase 
                 LPL 
               
               
                 P06881 
                 Calcitonin gene-related peptide 1 
                 CALCA 
               
               
                 P07093 
                 Glia-derived nexin 
                 SERPINE2 
               
               
                 P07098 
                 Gastric triacylglycerol lipase 
                 LIPF 
               
               
                 P07225 
                 Vitamin K-dependent protein S 
                 PROS1 
               
               
                 P07237 
                 Protein disulfide-isomerase 
                 P4HB 
               
               
                 P07288 
                 Prostate-specific antigen 
                 KLK3 
               
               
                 P07306 
                 Asialoglycoprotein receptor 1 
                 ASGR1 
               
               
                 P07355 
                 Annexin A2 
                 ANXA2 
               
               
                 P07357 
                 Complement component C8 alpha chain 
                 C8A 
               
               
                 P07358 
                 Complement component C8 beta chain 
                 C8B 
               
               
                 P07360 
                 Complement component C8 gamma chain 
                 C8G 
               
               
                 P07477 
                 Alpha-trypsin chain 2 
                 PRSS1 
               
               
                 P07478 
                 Trypsin-2 
                 PRSS2 
               
               
                 P07492 
                 Neuromedin-C 
                 GRP 
               
               
                 P07498 
                 Kappa-casein 
                 CSN3 
               
               
                 P07585 
                 Decorin 
                 DCN 
               
               
                 P07911 
                 Uromodulin 
                 UMOD 
               
               
                 P07942 
                 Laminin subunit beta-1 
                 LAMB1 
               
               
                 P07988 
                 Pulmonary surfactant-associated protein B 
                 SFTPB 
               
               
                 P07998 
                 Ribonuclease pancreatic 
                 RNASE1 
               
               
                 P08118 
                 Beta-microseminoprotein 
                 MSMB 
               
               
                 P08123 
                 Collagen alpha-2(I) chain 
                 COL1A2 
               
               
                 P08185 
                 Corticosteroid-binding globulin 
                 SERPINA6 
               
               
                 P08217 
                 Chymotrypsin-like elastase family member 2A 
                 CELA2A 
               
               
                 P08218 
                 Chymotrypsin-like elastase family member 2B 
                 CELA2B 
               
               
                 P08253 
                 72 kDa type IV collagenase 
                 MMP2 
               
               
                 P08254 
                 Stromelysin-1 
                 MMP3 
               
               
                 P08294 
                 Extracellular superoxide dismutase [Cu—Zn] 
                 SOD3 
               
               
                 P08476 
                 Inhibin beta A chain 
                 INHBA 
               
               
                 P08493 
                 Matrix Gla protein 
                 MGP 
               
               
                 P08572 
                 Collagen alpha-2(IV) chain 
                 COL4A2 
               
               
                 P08581 
                 Hepatocyte growth factor receptor 
                 MET 
               
               
                 P08603 
                 Complement factor H 
                 CFH 
               
               
                 P08620 
                 Fibroblast growth factor 4 
                 FGF4 
               
               
                 P08637 
                 Low affinity immunoglobulin gamma Fc region 
                 FCGR3A 
               
               
                   
                 receptor III-A 
               
               
                 P08697 
                 Alpha-2-antiplasmin 
                 SERPINF2 
               
               
                 P08700 
                 Interleukin-3 
                 IL3 
               
               
                 P08709 
                 Coagulation factor VII 
                 F7 
               
               
                 P08833 
                 Insulin-like growth factor-binding protein 1 
                 IGFBP1 
               
               
                 P08887 
                 Interleukin-6 receptor subunit alpha 
                 IL6R 
               
               
                 P08949 
                 Neuromedin-B-32 
                 NMB 
               
               
                 P08F94 
                 Fibrocystin 
                 PKHD1 
               
               
                 P09038 
                 Fibroblast growth factor 2 
                 FGF2 
               
               
                 P09228 
                 Cystatin-SA 
                 CST2 
               
               
                 P09237 
                 Matrilysin 
                 MMP7 
               
               
                 P09238 
                 Stromelysin-2 
                 MMP10 
               
               
                 P09341 
                 Growth-regulated alpha protein 
                 CXCL1 
               
               
                 P09382 
                 Galectin-1 
                 LGALS1 
               
               
                 P09466 
                 Glycodelin 
                 PAEP 
               
               
                 P09486 
                 SPARC 
                 SPARC 
               
               
                 P09529 
                 Inhibin beta B chain 
                 INHBB 
               
               
                 P09544 
                 Protein Wnt-2 
                 WNT2 
               
               
                 P09603 
                 Processed macrophage colony-stimulating factor 1 
                 CSF1 
               
               
                 P09681 
                 Gastric inhibitory polypeptide 
                 GIP 
               
               
                 P09683 
                 Secretin 
                 SCT 
               
               
                 P09919 
                 Granulocyte colony-stimulating factor 
                 CSF3 
               
               
                 P0C091 
                 FRAS1-related extracellular matrix protein 3 
                 FREM3 
               
               
                 P0C0L4 
                 C4d-A 
                 C4A 
               
               
                 P0C0L5 
                 Complement C4-B alpha chain 
                 C4B 
               
               
                 P0C0P6 
                 Neuropeptide S 
                 NPS 
               
               
                 P0C7L1 
                 Serine protease inhibitor Kazal-type 8 
                 SPINK8 
               
               
                 P0C862 
                 Complement C1q and tumor necrosis factor- 
                 C1QTNF9 
               
               
                   
                 related protein 9A 
               
               
                 P0C8F1 
                 Prostate and testis expressed protein 4 
                 PATE4 
               
               
                 P0CG01 
                 Gastrokine-3 
                 GKN3P 
               
               
                 P0CG36 
                 Cryptic family protein 1B 
                 CFC1B 
               
               
                 P0CG37 
                 Cryptic protein 
                 CFC1 
               
               
                 P0CJ68 
                 Humanin-like protein 1 
                 MTRNR2L1 
               
               
                 P0CJ69 
                 Humanin-like protein 2 
                 MTRNR2L2 
               
               
                 P0CJ70 
                 Humanin-like protein 3 
                 MTRNR2L3 
               
               
                 P0CJ71 
                 Humanin-like protein 4 
                 MTRNR2L4 
               
               
                 P0CJ72 
                 Humanin-like protein 5 
                 MTRNR2L5 
               
               
                 P0CJ73 
                 Humanin-like protein 6 
                 MTRNR2L6 
               
               
                 P0CJ74 
                 Humanin-like protein 7 
                 MTRNR2L7 
               
               
                 P0CJ75 
                 Humanin-like protein 8 
                 MTRNR2L8 
               
               
                 P0CJ76 
                 Humanin-like protein 9 
                 MTRNR2L9 
               
               
                 P0CJ77 
                 Humanin-like protein 10 
                 MTRNR2L10 
               
               
                 P0DJD7 
                 Pepsin A-4 
                 PGA4 
               
               
                 P0DJD8 
                 Pepsin A-3 
                 PGA3 
               
               
                 P0DJD9 
                 Pepsin A-5 
                 PGA5 
               
               
                 P0DJI8 
                 Amyloid protein A 
                 SAA1 
               
               
                 P0DJI9 
                 Serum amyloid A-2 protein 
                 SAA2 
               
               
                 P10082 
                 Peptide YY(3-36) 
                 PYY 
               
               
                 P10092 
                 Calcitonin gene-related peptide 2 
                 CALCB 
               
               
                 P10124 
                 Serglycin 
                 SRGN 
               
               
                 P10145 
                 MDNCF-a 
                 IL8 
               
               
                 P10147 
                 MIP-1-alpha(4-69) 
                 CCL3 
               
               
                 P10163 
                 Peptide P-D 
                 PRB4 
               
               
                 P10451 
                 Osteopontin 
                 SPP1 
               
               
                 P10599 
                 Thioredoxin 
                 TXN 
               
               
                 P10600 
                 Transforming growth factor beta-3 
                 TGFB3 
               
               
                 P10643 
                 Complement component C7 
                 C7 
               
               
                 P10645 
                 Vasostatin-2 
                 CHGA 
               
               
                 P10646 
                 Tissue factor pathway inhibitor 
                 TFPI 
               
               
                 P10720 
                 Platelet factor 4 variant(4-74) 
                 PF4V1 
               
               
                 P10745 
                 Retinol-binding protein 3 
                 RBP3 
               
               
                 P10767 
                 Fibroblast growth factor 6 
                 FGF6 
               
               
                 P10909 
                 Clusterin alpha chain 
                 CLU 
               
               
                 P10912 
                 Growth hormone receptor 
                 GHR 
               
               
                 P10915 
                 Hyaluronan and proteoglycan link protein 1 
                 HAPLN1 
               
               
                 P10966 
                 T-cell surface glycoprotein CD8 beta chain 
                 CD8B 
               
               
                 P10997 
                 Islet amyloid polypeptide 
                 IAPP 
               
               
                 P11047 
                 Laminin subunit gamma-1 
                 LAMC1 
               
               
                 P11150 
                 Hepatic triacylglycerol lipase 
                 LIPC 
               
               
                 P11226 
                 Mannose-binding protein C 
                 MBL2 
               
               
                 P11464 
                 Pregnancy-specific beta-1-glycoprotein 1 
                 PSG1 
               
               
                 P11465 
                 Pregnancy-specific beta-1-glycoprotein 2 
                 PSG2 
               
               
                 P11487 
                 Fibroblast growth factor 3 
                 FGF3 
               
               
                 P11597 
                 Cholesteryl ester transfer protein 
                 CETP 
               
               
                 P11684 
                 Uteroglobin 
                 SCGB1A1 
               
               
                 P11686 
                 Pulmonary surfactant-associated protein C 
                 SFTPC 
               
               
                 P12034 
                 Fibroblast growth factor 5 
                 FGF5 
               
               
                 P12107 
                 Collagen alpha-1(XI) chain 
                 COL11A1 
               
               
                 P12109 
                 Collagen alpha-1(VI) chain 
                 COL6A1 
               
               
                 P12110 
                 Collagen alpha-2(VI) chain 
                 COL6A2 
               
               
                 P12111 
                 Collagen alpha-3(VI) chain 
                 COL6A3 
               
               
                 P12259 
                 Coagulation factor V 
                 F5 
               
               
                 P12272 
                 PTHrP[1-36] 
                 PTHLH 
               
               
                 P12273 
                 Prolactin-inducible protein 
                 PIP 
               
               
                 P12544 
                 Granzyme A 
                 GZMA 
               
               
                 P12643 
                 Bone morphogenetic protein 2 
                 BMP2 
               
               
                 P12644 
                 Bone morphogenetic protein 4 
                 BMP4 
               
               
                 P12645 
                 Bone morphogenetic protein 3 
                 BMP3 
               
               
                 P12724 
                 Eosinophil cationic protein 
                 RNASE3 
               
               
                 P12821 
                 Angiotensin-converting enzyme, soluble form 
                 ACE 
               
               
                 P12838 
                 Neutrophil defensin 4 
                 DEFA4 
               
               
                 P12872 
                 Motilin 
                 MLN 
               
               
                 P13232 
                 Interleukin-7 
                 IL7 
               
               
                 P13236 
                 C-C motif chemokine 4 
                 CCL4 
               
               
                 P13284 
                 Gamma-interferon-inducible lysosomal thiol 
                 IFI30 
               
               
                   
                 reductase 
               
               
                 P13500 
                 C-C motif chemokine 2 
                 CCL2 
               
               
                 P13501 
                 C-C motif chemokine 5 
                 CCL5 
               
               
                 P13521 
                 Secretogranin-2 
                 SCG2 
               
               
                 P13591 
                 Neural cell adhesion molecule 1 
                 NCAM1 
               
               
                 P13611 
                 Versican core protein 
                 VCAN 
               
               
                 P13671 
                 Complement component C6 
                 C6 
               
               
                 P13688 
                 Carcinoembryonic antigen-related cell adhesion 
                 CEACAM1 
               
               
                   
                 molecule 1 
               
               
                 P13725 
                 Oncostatin-M 
                 OSM 
               
               
                 P13726 
                 Tissue factor 
                 F3 
               
               
                 P13727 
                 Eosinophil granule major basic protein 
                 PRG2 
               
               
                 P13942 
                 Collagen alpha-2(XI) chain 
                 COL11A2 
               
               
                 P13987 
                 CD59 glycoprotein 
                 CD59 
               
               
                 P14138 
                 Endothelin-3 
                 EDN3 
               
               
                 P14174 
                 Macrophage migration inhibitory factor 
                 MIF 
               
               
                 P14207 
                 Folate receptor beta 
                 FOLR2 
               
               
                 P14222 
                 Perforin-1 
                 PRF1 
               
               
                 P14543 
                 Nidogen-1 
                 NID1 
               
               
                 P14555 
                 Phospholipase A2, membrane associated 
                 PLA2G2A 
               
               
                 P14625 
                 Endoplasmin 
                 HSP90B1 
               
               
                 P14735 
                 Insulin-degrading enzyme 
                 IDE 
               
               
                 P14778 
                 Interleukin-1 receptor type 1, soluble form 
                 IL1R1 
               
               
                 P14780 
                 82 kDa matrix metalloproteinase-9 
                 MMP9 
               
               
                 P15018 
                 Leukemia inhibitory factor 
                 LIF 
               
               
                 P15085 
                 Carboxypeptidase A1 
                 CPA1 
               
               
                 P15086 
                 Carboxypeptidase B 
                 CPB1 
               
               
                 P15151 
                 Poliovirus receptor 
                 PVR 
               
               
                 P15169 
                 Carboxypeptidase N catalytic chain 
                 CPN1 
               
               
                 P15248 
                 Interleukin-9 
                 IL9 
               
               
                 P15291 
                 N-acetyllactosamine synthase 
                 B4GALT1 
               
               
                 P15309 
                 PAPf39 
                 ACPP 
               
               
                 P15328 
                 Folate receptor alpha 
                 FOLR1 
               
               
                 P15374 
                 Ubiquitin carboxyl-terminal hydrolase isozyme L3 
                 UCHL3 
               
               
                 P15502 
                 Elastin 
                 ELN 
               
               
                 P15509 
                 Granulocyte-macrophage colony-stimulating 
                 CSF2RA 
               
               
                   
                 factor receptor subunit alpha 
               
               
                 P15515 
                 Histatin-1 
                 HTN1 
               
               
                 P15516 
                 His3-(31-51)-peptide 
                 HTN3 
               
               
                 P15692 
                 Vascular endothelial growth factor A 
                 VEGFA 
               
               
                 P15814 
                 Immunoglobulin lambda-like polypeptide 1 
                 IGLL1 
               
               
                 P15907 
                 Beta-galactoside alpha-2,6-sialyltransferase 1 
                 ST6GAL1 
               
               
                 P15941 
                 Mucin-1 subunit beta 
                 MUC1 
               
               
                 P16035 
                 Metalloproteinase inhibitor 2 
                 TIMP2 
               
               
                 P16112 
                 Aggrecan core protein 2 
                 ACAN 
               
               
                 P16233 
                 Pancreatic triacylglycerol lipase 
                 PNLIP 
               
               
                 P16442 
                 Histo-blood group ABO system transferase 
                 ABO 
               
               
                 P16471 
                 Prolactin receptor 
                 PRLR 
               
               
                 P16562 
                 Cysteine-rich secretory protein 2 
                 CRISP2 
               
               
                 P16619 
                 C-C motif chemokine 3-like 1 
                 CCL3L1 
               
               
                 P16860 
                 BNP(3-29) 
                 NPPB 
               
               
                 P16870 
                 Carboxypeptidase E 
                 CPE 
               
               
                 P16871 
                 Interleukin-7 receptor subunit alpha 
                 IL7R 
               
               
                 P17213 
                 Bactericidal permeability-increasing protein 
                 BPI 
               
               
                 P17538 
                 Chymotrypsinogen B 
                 CTRB1 
               
               
                 P17931 
                 Galectin-3 
                 LGALS3 
               
               
                 P17936 
                 Insulin-like growth factor-binding protein 3 
                 IGFBP3 
               
               
                 P17948 
                 Vascular endothelial growth factor receptor 1 
                 FLT1 
               
               
                 P18065 
                 Insulin-like growth factor-binding protein 2 
                 IGFBP2 
               
               
                 P18075 
                 Bone morphogenetic protein 7 
                 BMP7 
               
               
                 P18428 
                 Lipopolysaccharide-binding protein 
                 LBP 
               
               
                 P18509 
                 PACAP-related peptide 
                 ADCYAP1 
               
               
                 P18510 
                 Interleukin-1 receptor antagonist protein 
                 IL1RN 
               
               
                 P18827 
                 Syndecan-1 
                 SDC1 
               
               
                 P19021 
                 Peptidylglycine alpha-hydroxylating 
                 PAM 
               
               
                   
                 monooxygenase 
               
               
                 P19235 
                 Erythropoietin receptor 
                 EPOR 
               
               
                 P19438 
                 Tumor necrosis factor-binding protein 1 
                 TNFRSF1A 
               
               
                 P19652 
                 Alpha-1-acid glycoprotein 2 
                 ORM2 
               
               
                 P19801 
                 Amiloride-sensitive amine oxidase [copper- 
                 ABP1 
               
               
                   
                 containing] 
               
               
                 P19823 
                 Inter-alpha-trypsin inhibitor heavy chain H2 
                 ITIH2 
               
               
                 P19827 
                 Inter-alpha-trypsin inhibitor heavy chain H1 
                 ITIH1 
               
               
                 P19835 
                 Bile salt-activated lipase 
                 CEL 
               
               
                 P19875 
                 C-X-C motif chemokine 2 
                 CXCL2 
               
               
                 P19876 
                 C-X-C motif chemokine 3 
                 CXCL3 
               
               
                 P19883 
                 Follistatin 
                 FST 
               
               
                 P19957 
                 Elafin 
                 PI3 
               
               
                 P19961 
                 Alpha-amylase 2B 
                 AMY2B 
               
               
                 P20061 
                 Transcobalamin-1 
                 TCN1 
               
               
                 P20062 
                 Transcobalamin-2 
                 TCN2 
               
               
                 P20142 
                 Gastricsin 
                 PGC 
               
               
                 P20155 
                 Serine protease inhibitor Kazal-type 2 
                 SPINK2 
               
               
                 P20231 
                 Tryptase beta-2 
                 TPSB2 
               
               
                 P20333 
                 Tumor necrosis factor receptor superfamily 
                 TNFRSF1B 
               
               
                   
                 member 1B 
               
               
                 P20366 
                 Substance P 
                 TAC1 
               
               
                 P20382 
                 Melanin-concentrating hormone 
                 PMCH 
               
               
                 P20396 
                 Thyroliberin 
                 TRH 
               
               
                 P20742 
                 Pregnancy zone protein 
                 PZP 
               
               
                 P20774 
                 Mimecan 
                 OGN 
               
               
                 P20783 
                 Neurotrophin-3 
                 NTF3 
               
               
                 P20800 
                 Endothelin-2 
                 EDN2 
               
               
                 P20809 
                 Interleukin-11 
                 IL11 
               
               
                 P20827 
                 Ephrin-A1 
                 EFNA1 
               
               
                 P20849 
                 Collagen alpha-1(IX) chain 
                 COL9A1 
               
               
                 P20851 
                 C4b-binding protein beta chain 
                 C4BPB 
               
               
                 P20908 
                 Collagen alpha-1(V) chain 
                 COL5A1 
               
               
                 P21128 
                 Poly(U)-specific endoribonuclease 
                 ENDOU 
               
               
                 P21246 
                 Pleiotrophin 
                 PTN 
               
               
                 P21583 
                 Kit ligand 
                 KITLG 
               
               
                 P21741 
                 Midkine 
                 MDK 
               
               
                 P21754 
                 Zona pellucida sperm-binding protein 3 
                 ZP3 
               
               
                 P21781 
                 Fibroblast growth factor 7 
                 FGF7 
               
               
                 P21802 
                 Fibroblast growth factor receptor 2 
                 FGFR2 
               
               
                 P21810 
                 Biglycan 
                 BGN 
               
               
                 P21815 
                 Bone sialoprotein 2 
                 IBSP 
               
               
                 P21860 
                 Receptor tyrosine-protein kinase erbB-3 
                 ERBB3 
               
               
                 P21941 
                 Cartilage matrix protein 
                 MATN1 
               
               
                 P22003 
                 Bone morphogenetic protein 5 
                 BMP5 
               
               
                 P22004 
                 Bone morphogenetic protein 6 
                 BMP6 
               
               
                 P22079 
                 Lactoperoxidase 
                 LPO 
               
               
                 P22105 
                 Tenascin-X 
                 TNXB 
               
               
                 P22301 
                 Interleukin-10 
                 IL10 
               
               
                 P22303 
                 Acetylcholinesterase 
                 ACHE 
               
               
                 P22352 
                 Glutathione peroxidase 3 
                 GPX3 
               
               
                 P22362 
                 C-C motif chemokine 1 
                 CCL1 
               
               
                 P22455 
                 Fibroblast growth factor receptor 4 
                 FGFR4 
               
               
                 P22466 
                 Galanin message-associated peptide 
                 GAL 
               
               
                 P22692 
                 Insulin-like growth factor-binding protein 4 
                 IGFBP4 
               
               
                 P22749 
                 Granulysin 
                 GNLY 
               
               
                 P22792 
                 Carboxypeptidase N subunit 2 
                 CPN2 
               
               
                 P22891 
                 Vitamin K-dependent protein Z 
                 PROZ 
               
               
                 P22894 
                 Neutrophil collagenase 
                 MMP8 
               
               
                 P23142 
                 Fibulin-1 
                 FBLN1 
               
               
                 P23280 
                 Carbonic anhydrase 6 
                 CA6 
               
               
                 P23352 
                 Anosmin-1 
                 KAL1 
               
               
                 P23435 
                 Cerebellin-1 
                 CBLN1 
               
               
                 P23560 
                 Brain-derived neurotrophic factor 
                 BDNF 
               
               
                 P23582 
                 C-type natriuretic peptide 
                 NPPC 
               
               
                 P23946 
                 Chymase 
                 CMA1 
               
               
                 P24043 
                 Laminin subunit alpha-2 
                 LAMA2 
               
               
                 P24071 
                 Immunoglobulin alpha Fc receptor 
                 FCAR 
               
               
                 P24347 
                 Stromelysin-3 
                 MMP11 
               
               
                 P24387 
                 Corticotropin-releasing factor-binding protein 
                 CRHBP 
               
               
                 P24592 
                 Insulin-like growth factor-binding protein 6 
                 IGFBP6 
               
               
                 P24593 
                 Insulin-like growth factor-binding protein 5 
                 IGFBP5 
               
               
                 P24821 
                 Tenascin 
                 TNC 
               
               
                 P24855 
                 Deoxyribonuclease-1 
                 DNASE1 
               
               
                 P25067 
                 Collagen alpha-2(VIII) chain 
                 COL8A2 
               
               
                 P25311 
                 Zinc-alpha-2-glycoprotein 
                 AZGP1 
               
               
                 P25391 
                 Laminin subunit alpha-1 
                 LAMA1 
               
               
                 P25445 
                 Tumor necrosis factor receptor superfamily 
                 FAS 
               
               
                   
                 member 6 
               
               
                 P25940 
                 Collagen alpha-3(V) chain 
                 COL5A3 
               
               
                 P25942 
                 Tumor necrosis factor receptor superfamily 
                 CD40 
               
               
                   
                 member 5 
               
               
                 P26022 
                 Pentraxin-related protein PTX3 
                 PTX3 
               
               
                 P26927 
                 Hepatocyte growth factor-like protein beta chain 
                 MST1 
               
               
                 P27169 
                 Serum paraoxonase/arylesterase 1 
                 PON1 
               
               
                 P27352 
                 Gastric intrinsic factor 
                 GIF 
               
               
                 P27487 
                 Dipeptidyl peptidase 4 membrane form 
                 DPP4 
               
               
                 P27539 
                 Embryonic growth/differentiation factor 1 
                 GDF1 
               
               
                 P27658 
                 Vastatin 
                 COL8A1 
               
               
                 P27797 
                 Calreticulin 
                 CALR 
               
               
                 P27918 
                 Properdin 
                 CFP 
               
               
                 P28039 
                 Acyloxyacyl hydrolase 
                 AOAH 
               
               
                 P28300 
                 Protein-lysine 6-oxidase 
                 LOX 
               
               
                 P28325 
                 Cystatin-D 
                 CST5 
               
               
                 P28799 
                 Granulin-1 
                 GRN 
               
               
                 P29122 
                 Proprotein convertase subtilisin/kexin type 6 
                 PCSK6 
               
               
                 P29279 
                 Connective tissue growth factor 
                 CTGF 
               
               
                 P29320 
                 Ephrin type-A receptor 3 
                 EPHA3 
               
               
                 P29400 
                 Collagen alpha-5(IV) chain 
                 COL4A5 
               
               
                 P29459 
                 Interleukin-12 subunit alpha 
                 IL12A 
               
               
                 P29460 
                 Interleukin-12 subunit beta 
                 IL12B 
               
               
                 P29508 
                 Serpin B3 
                 SERPINB3 
               
               
                 P29622 
                 Kallistatin 
                 SERPINA4 
               
               
                 P29965 
                 CD40 ligand, soluble form 
                 CD40LG 
               
               
                 P30990 
                 Neurotensin/neuromedin N 
                 NTS 
               
               
                 P31025 
                 Lipocalin-1 
                 LCN1 
               
               
                 P31151 
                 Protein S100-A7 
                 S100A7 
               
               
                 P31371 
                 Fibroblast growth factor 9 
                 FGF9 
               
               
                 P31431 
                 Syndecan-4 
                 SDC4 
               
               
                 P31947 
                 14-3-3 protein sigma 
                 SFN 
               
               
                 P32455 
                 Interferon-induced guanylate-binding protein 1 
                 GBP1 
               
               
                 P32881 
                 Interferon alpha-8 
                 IFNA8 
               
               
                 P34096 
                 Ribonuclease 4 
                 RNASE4 
               
               
                 P34130 
                 Neurotrophin-4 
                 NTF4 
               
               
                 P34820 
                 Bone morphogenetic protein 8B 
                 BMP8B 
               
               
                 P35030 
                 Trypsin-3 
                 PRSS3 
               
               
                 P35052 
                 Secreted glypican-1 
                 GPC1 
               
               
                 P35070 
                 Betacellulin 
                 BTC 
               
               
                 P35225 
                 Interleukin-13 
                 IL13 
               
               
                 P35247 
                 Pulmonary surfactant-associated protein D 
                 SFTPD 
               
               
                 P35318 
                 ADM 
                 ADM 
               
               
                 P35542 
                 Serum amyloid A-4 protein 
                 SAA4 
               
               
                 P35555 
                 Fibrillin-1 
                 FBN1 
               
               
                 P35556 
                 Fibrillin-2 
                 FBN2 
               
               
                 P35625 
                 Metalloproteinase inhibitor 3 
                 TIMP3 
               
               
                 P35858 
                 Insulin-like growth factor-binding protein complex 
                 IGFALS 
               
               
                   
                 acid labile subunit 
               
               
                 P35916 
                 Vascular endothelial growth factor receptor 3 
                 FLT4 
               
               
                 P35968 
                 Vascular endothelial growth factor receptor 2 
                 KDR 
               
               
                 P36222 
                 Chitinase-3-like protein 1 
                 CHI3L1 
               
               
                 P36952 
                 Serpin B5 
                 SERPINB5 
               
               
                 P36955 
                 Pigment epithelium-derived factor 
                 SERPINF1 
               
               
                 P36980 
                 Complement factor H-related protein 2 
                 CFHR2 
               
               
                 P39059 
                 Collagen alpha-1(XV) chain 
                 COL15A1 
               
               
                 P39060 
                 Collagen alpha-1(XVIII) chain 
                 COL18A1 
               
               
                 P39877 
                 Calcium-dependent phospholipase A2 
                 PLA2G5 
               
               
                 P39900 
                 Macrophage metalloelastase 
                 MMP12 
               
               
                 P39905 
                 Glial cell line-derived neurotrophic factor 
                 GDNF 
               
               
                 P40225 
                 Thrombopoietin 
                 THPO 
               
               
                 P40967 
                 M-alpha 
                 PMEL 
               
               
                 P41159 
                 Leptin 
                 LEP 
               
               
                 P41221 
                 Protein Wnt-5a 
                 WNT5A 
               
               
                 P41222 
                 Prostaglandin-H2 D-isomerase 
                 PTGDS 
               
               
                 P41271 
                 Neuroblastoma suppressor of tumorigenicity 1 
                 NBL1 
               
               
                 P41439 
                 Folate receptor gamma 
                 FOLR3 
               
               
                 P42127 
                 Agouti-signaling protein 
                 ASIP 
               
               
                 P42702 
                 Leukemia inhibitory factor receptor 
                 LIFR 
               
               
                 P42830 
                 ENA-78(9-78) 
                 CXCL5 
               
               
                 P43026 
                 Growth/differentiation factor 5 
                 GDF5 
               
               
                 P43251 
                 Biotinidase 
                 BTD 
               
               
                 P43652 
                 Afamin 
                 AFM 
               
               
                 P45452 
                 Collagenase 3 
                 MMP13 
               
               
                 P47710 
                 Casoxin-D 
                 CSN1S1 
               
               
                 P47929 
                 Galectin-7 
                 LGALS7B 
               
               
                 P47972 
                 Neuronal pentraxin-2 
                 NPTX2 
               
               
                 P47989 
                 Xanthine oxidase 
                 XDH 
               
               
                 P47992 
                 Lymphotactin 
                 XCL1 
               
               
                 P48023 
                 Tumor necrosis factor ligand superfamily member 
                 FASLG 
               
               
                   
                 6, membrane form 
               
               
                 P48052 
                 Carboxypeptidase A2 
                 CPA2 
               
               
                 P48061 
                 Stromal cell-derived factor 1 
                 CXCL12 
               
               
                 P48304 
                 Lithostathine-1-beta 
                 REG1B 
               
               
                 P48307 
                 Tissue factor pathway inhibitor 2 
                 TFPI2 
               
               
                 P48357 
                 Leptin receptor 
                 LEPR 
               
               
                 P48594 
                 Serpin B4 
                 SERPINB4 
               
               
                 P48645 
                 Neuromedin-U-25 
                 NMU 
               
               
                 P48740 
                 Mannan-binding lectin serine protease 1 
                 MASP1 
               
               
                 P48745 
                 Protein NOV homolog 
                 NOV 
               
               
                 P48960 
                 CD97 antigen subunit beta 
                 CD97 
               
               
                 P49223 
                 Kunitz-type protease inhibitor 3 
                 SPINT3 
               
               
                 P49747 
                 Cartilage oligomeric matrix protein 
                 COMP 
               
               
                 P49763 
                 Placenta growth factor 
                 PGF 
               
               
                 P49765 
                 Vascular endothelial growth factor B 
                 VEGFB 
               
               
                 P49767 
                 Vascular endothelial growth factor C 
                 VEGFC 
               
               
                 P49771 
                 Fms-related tyrosine kinase 3 ligand 
                 FLT3LG 
               
               
                 P49862 
                 Kallikrein-7 
                 KLK7 
               
               
                 P49863 
                 Granzyme K 
                 GZMK 
               
               
                 P49908 
                 Selenoprotein P 
                 SEPP1 
               
               
                 P49913 
                 Antibacterial protein FALL-39 
                 CAMP 
               
               
                 P50607 
                 Tubby protein homolog 
                 TUB 
               
               
                 P51124 
                 Granzyme M 
                 GZMM 
               
               
                 P51512 
                 Matrix metalloproteinase-16 
                 MMP16 
               
               
                 P51654 
                 Glypican-3 
                 GPC3 
               
               
                 P51671 
                 Eotaxin 
                 CCL11 
               
               
                 P51884 
                 Lumican 
                 LUM 
               
               
                 P51888 
                 Prolargin 
                 PRELP 
               
               
                 P52798 
                 Ephrin-A4 
                 EFNA4 
               
               
                 P52823 
                 Stanniocalcin-1 
                 STC1 
               
               
                 P53420 
                 Collagen alpha-4(IV) chain 
                 COL4A4 
               
               
                 P53621 
                 Coatomer subunit alpha 
                 COPA 
               
               
                 P54108 
                 Cysteine-rich secretory protein 3 
                 CRISP3 
               
               
                 P54315 
                 Pancreatic lipase-related protein 1 
                 PNLIPRP1 
               
               
                 P54317 
                 Pancreatic lipase-related protein 2 
                 PNLIPRP2 
               
               
                 P54793 
                 Arylsulfatase F 
                 ARSF 
               
               
                 P55000 
                 Secreted Ly-6/uPAR-related protein 1 
                 SLURP 1 
               
               
                 P55001 
                 Microfibrillar-associated protein 2 
                 MFAP2 
               
               
                 P55056 
                 Apolipoprotein C-IV 
                 APOC4 
               
               
                 P55058 
                 Phospholipid transfer protein 
                 PLTP 
               
               
                 P55075 
                 Fibroblast growth factor 8 
                 FGF8 
               
               
                 P55081 
                 Microfibrillar-associated protein 1 
                 MFAP1 
               
               
                 P55083 
                 Microfibril-associated glycoprotein 4 
                 MFAP4 
               
               
                 P55107 
                 Bone morphogenetic protein 3B 
                 GDF10 
               
               
                 P55145 
                 Mesencephalic astrocyte-derived neurotrophic 
                 MANF 
               
               
                   
                 factor 
               
               
                 P55259 
                 Pancreatic secretory granule membrane major 
                 GP2 
               
               
                   
                 glycoprotein GP2 
               
               
                 P55268 
                 Laminin subunit beta-2 
                 LAMB2 
               
               
                 P55773 
                 CCL23(30-99) 
                 CCL23 
               
               
                 P55774 
                 C-C motif chemokine 18 
                 CCL18 
               
               
                 P55789 
                 FAD-linked sulfhydryl oxidase ALR 
                 GFER 
               
               
                 P56703 
                 Proto-oncogene Wnt-3 
                 WNT3 
               
               
                 P56704 
                 Protein Wnt-3a 
                 WNT3A 
               
               
                 P56705 
                 Protein Wnt-4 
                 WNT4 
               
               
                 P56706 
                 Protein Wnt-7b 
                 WNT7B 
               
               
                 P56730 
                 Neurotrypsin 
                 PRSS12 
               
               
                 P56851 
                 Epididymal secretory protein E3-beta 
                 EDDM3B 
               
               
                 P56975 
                 Neuregulin-3 
                 NRG3 
               
               
                 P58062 
                 Serine protease inhibitor Kazal-type 7 
                 SPINK7 
               
               
                 P58215 
                 Lysyl oxidase homolog 3 
                 LOXL3 
               
               
                 P58294 
                 Prokineticin-1 
                 PROK1 
               
               
                 P58335 
                 Anthrax toxin receptor 2 
                 ANTXR2 
               
               
                 P58397 
                 A disintegrin and metalloproteinase with 
                 ADAMTS12 
               
               
                   
                 thrombospondin motifs 12 
               
               
                 P58417 
                 Neurexophilin-1 
                 NXPH1 
               
               
                 P58499 
                 Protein FAM3B 
                 FAM3B 
               
               
                 P59510 
                 A disintegrin and metalloproteinase with 
                 ADAMTS20 
               
               
                   
                 thrombospondin motifs 20 
               
               
                 P59665 
                 Neutrophil defensin 1 
                 DEFA1B 
               
               
                 P59666 
                 Neutrophil defensin 3 
                 DEFA3 
               
               
                 P59796 
                 Glutathione peroxidase 6 
                 GPX6 
               
               
                 P59826 
                 BPI fold-containing family B member 3 
                 BPIFB3 
               
               
                 P59827 
                 BPI fold-containing family B member 4 
                 BPIFB4 
               
               
                 P59861 
                 Beta-defensin 131 
                 DEFB131 
               
               
                 P60022 
                 Beta-defensin 1 
                 DEFB1 
               
               
                 P60153 
                 Inactive ribonuclease-like protein 9 
                 RNASE9 
               
               
                 P60827 
                 Complement C1q tumor necrosis factor-related 
                 C1QTNF8 
               
               
                   
                 protein 8 
               
               
                 P60852 
                 Zona pellucida sperm-binding protein 1 
                 ZP1 
               
               
                 P60985 
                 Keratinocyte differentiation-associated protein 
                 KRTDAP 
               
               
                 P61109 
                 Kidney androgen-regulated protein 
                 KAP 
               
               
                 P61278 
                 Somatostatin-14 
                 SST 
               
               
                 P61366 
                 Osteocrin 
                 OSTN 
               
               
                 P61626 
                 Lysozyme C 
                 LYZ 
               
               
                 P61769 
                 Beta-2-microglobulin 
                 B2M 
               
               
                 P61812 
                 Transforming growth factor beta-2 
                 TGFB2 
               
               
                 P61916 
                 Epididymal secretory protein E1 
                 NPC2 
               
               
                 P62502 
                 Epididymal-specific lipocalin-6 
                 LCN6 
               
               
                 P62937 
                 Peptidyl-prolyl cis-trans isomerase A 
                 PPIA 
               
               
                 P67809 
                 Nuclease-sensitive element-binding protein 1 
                 YBX1 
               
               
                 P67812 
                 Signal peptidase complex catalytic subunit 
                 SEC11A 
               
               
                   
                 SEC11A 
               
               
                 P78310 
                 Coxsackievirus and adenovirus receptor 
                 CXADR 
               
               
                 P78333 
                 Secreted glypican-5 
                 GPC5 
               
               
                 P78380 
                 Oxidized low-density lipoprotein receptor 1 
                 OLR1 
               
               
                 P78423 
                 Processed fractalkine 
                 CX3CL1 
               
               
                 P78509 
                 Reelin 
                 RELN 
               
               
                 P78556 
                 CCL20(2-70) 
                 CCL20 
               
               
                 P80075 
                 MCP-2(6-76) 
                 CCL8 
               
               
                 P80098 
                 C-C motif chemokine 7 
                 CCL7 
               
               
                 P80108 
                 Phosphatidylinositol-glycan-specific 
                 GPLD1 
               
               
                   
                 phospholipase D 
               
               
                 P80162 
                 C-X-C motif chemokine 6 
                 CXCL6 
               
               
                 P80188 
                 Neutrophil gelatinase-associated lipocalin 
                 LCN2 
               
               
                 P80303 
                 Nucleobindin-2 
                 NUCB2 
               
               
                 P80511 
                 Calcitermin 
                 S100A12 
               
               
                 P81172 
                 Hepcidin-25 
                 HAMP 
               
               
                 P81277 
                 Prolactin-releasing peptide 
                 PRLH 
               
               
                 P81534 
                 Beta-defensin 103 
                 DEFB103A 
               
               
                 P81605 
                 Dermcidin 
                 DCD 
               
               
                 P82279 
                 Protein crumbs homolog 1 
                 CRB1 
               
               
                 P82987 
                 ADAMTS-like protein 3 
                 ADAMTSL3 
               
               
                 P83105 
                 Serine protease HTRA4 
                 HTRA4 
               
               
                 P83110 
                 Serine protease HTRA3 
                 HTRA3 
               
               
                 P83859 
                 Orexigenic neuropeptide QRFP 
                 QRFP 
               
               
                 P98088 
                 Mucin-5AC 
                 MUC5AC 
               
               
                 P98095 
                 Fibulin-2 
                 FBLN2 
               
               
                 P98160 
                 Basement membrane-specific heparan sulfate 
                 HSPG2 
               
               
                   
                 proteoglycan core protein 
               
               
                 P98173 
                 Protein FAM3A 
                 FAM3A 
               
               
                 Q00604 
                 Norrin 
                 NDP 
               
               
                 Q00796 
                 Sorbitol dehydrogenase 
                 SORD 
               
               
                 Q00887 
                 Pregnancy-specific beta-1-glycoprotein 9 
                 PSG9 
               
               
                 Q00888 
                 Pregnancy-specific beta-1-glycoprotein 4 
                 PSG4 
               
               
                 Q00889 
                 Pregnancy-specific beta-1-glycoprotein 6 
                 PSG6 
               
               
                 Q01523 
                 HD5(56-94) 
                 DEFA5 
               
               
                 Q01524 
                 Defensin-6 
                 DEFA6 
               
               
                 Q01955 
                 Collagen alpha-3(IV) chain 
                 COL4A3 
               
               
                 Q02297 
                 Pro-neuregulin-1, membrane-bound isoform 
                 NRG1 
               
               
                 Q02325 
                 Plasminogen-like protein B 
                 PLGLB1 
               
               
                 Q02383 
                 Semenogelin-2 
                 SEMG2 
               
               
                 Q02388 
                 Collagen alpha-1(VII) chain 
                 COL7A1 
               
               
                 Q02505 
                 Mucin-3A 
                 MUC3A 
               
               
                 Q02509 
                 Otoconin-90 
                 OC90 
               
               
                 Q02747 
                 Guanylin 
                 GUCA2A 
               
               
                 Q02763 
                 Angiopoietin-1 receptor 
                 TEK 
               
               
                 Q02817 
                 Mucin-2 
                 MUC2 
               
               
                 Q02985 
                 Complement factor H-related protein 3 
                 CFHR3 
               
               
                 Q03167 
                 Transforming growth factor beta receptor type 3 
                 TGFBR3 
               
               
                 Q03403 
                 Trefoil factor 2 
                 TFF2 
               
               
                 Q03405 
                 Urokinase plasminogen activator surface receptor 
                 PLAUR 
               
               
                 Q03591 
                 Complement factor H-related protein 1 
                 CFHR1 
               
               
                 Q03692 
                 Collagen alpha-1(X) chain 
                 COL10A1 
               
               
                 Q04118 
                 Basic salivary proline-rich protein 3 
                 PRB3 
               
               
                 Q04756 
                 Hepatocyte growth factor activator short chain 
                 HGFAC 
               
               
                 Q04900 
                 Sialomucin core protein 24 
                 CD164 
               
               
                 Q05315 
                 Eosinophil lysophospholipase 
                 CLC 
               
               
                 Q05707 
                 Collagen alpha-1(XIV) chain 
                 COL14A1 
               
               
                 Q05996 
                 Processed zona pellucida sperm-binding protein 2 
                 ZP2 
               
               
                 Q06033 
                 Inter-alpha-trypsin inhibitor heavy chain H3 
                 ITIH3 
               
               
                 Q06141 
                 Regenerating islet-derived protein 3-alpha 
                 REG3A 
               
               
                 Q06828 
                 Fibromodulin 
                 FMOD 
               
               
                 Q07092 
                 Collagen alpha-1(XVI) chain 
                 COL16A1 
               
               
                 Q07325 
                 C-X-C motif chemokine 9 
                 CXCL9 
               
               
                 Q07507 
                 Dermatopontin 
                 DPT 
               
               
                 Q075Z2 
                 Binder of sperm protein homolog 1 
                 BSPH1 
               
               
                 Q07654 
                 Trefoil factor 3 
                 TFF3 
               
               
                 Q07699 
                 Sodium channel subunit beta-1 
                 SCN1B 
               
               
                 Q08345 
                 Epithelial discoidin domain-containing receptor 1 
                 DDR1 
               
               
                 Q08380 
                 Galectin-3-binding protein 
                 LGALS3BP 
               
               
                 Q08397 
                 Lysyl oxidase homolog 1 
                 LOXL1 
               
               
                 Q08431 
                 Lactadherin 
                 MFGE8 
               
               
                 Q08629 
                 Testican-1 
                 SPOCK1 
               
               
                 Q08648 
                 Sperm-associated antigen 11B 
                 SPAG11B 
               
               
                 Q08830 
                 Fibrinogen-like protein 1 
                 FGL1 
               
               
                 Q10471 
                 Polypeptide N-acetylgalactosaminyltransferase 2 
                 GALNT2 
               
               
                 Q10472 
                 Polypeptide N-acetylgalactosaminyltransferase 1 
                 GALNT1 
               
               
                 Q11201 
                 CMP-N-acetylneuraminate-beta-galactosamide- 
                 ST3GAL1 
               
               
                   
                 alpha-2,3-sialyltransferase 1 
               
               
                 Q11203 
                 CMP-N-acetylneuraminate-beta-1,4-galactoside 
                 ST3GAL3 
               
               
                   
                 alpha-2,3-sialyltransferase 
               
               
                 Q11206 
                 CMP-N-acetylneuraminate-beta-galactosamide- 
                 ST3GAL4 
               
               
                   
                 alpha-2,3-sialyltransferase 4 
               
               
                 Q12794 
                 Hyaluronidase-1 
                 HYAL1 
               
               
                 Q12805 
                 EGF-containing fibulin-like extracellular matrix 
                 EFEMP1 
               
               
                   
                 protein 1 
               
               
                 Q12836 
                 Zona pellucida sperm-binding protein 4 
                 ZP4 
               
               
                 Q12841 
                 Follistatin-related protein 1 
                 FSTL1 
               
               
                 Q12904 
                 Aminoacyl tRNA synthase complex-interacting 
                 AIMP1 
               
               
                   
                 multifunctional protein 1 
               
               
                 Q13018 
                 Soluble secretory phospholipase A2 receptor 
                 PLA2R1 
               
               
                 Q13072 
                 B melanoma antigen 1 
                 BAGE 
               
               
                 Q13093 
                 Platelet-activating factor acetylhydrolase 
                 PLA2G7 
               
               
                 Q13103 
                 Secreted phosphoprotein 24 
                 SPP2 
               
               
                 Q13162 
                 Peroxiredoxin-4 
                 PRDX4 
               
               
                 Q13201 
                 Platelet glycoprotein Ia* 
                 MMRN1 
               
               
                 Q13214 
                 Semaphorin-3B 
                 SEMA3B 
               
               
                 Q13219 
                 Pappalysin-1 
                 PAPPA 
               
               
                 Q13231 
                 Chitotriosidase-1 
                 CHIT1 
               
               
                 Q13253 
                 Noggin 
                 NOG 
               
               
                 Q13261 
                 Interleukin-15 receptor subunit alpha 
                 IL15RA 
               
               
                 Q13275 
                 Semaphorin-3F 
                 SEMA3F 
               
               
                 Q13291 
                 Signaling lymphocytic activation molecule 
                 SLAMF1 
               
               
                 Q13316 
                 Dentin matrix acidic phosphoprotein 1 
                 DMP1 
               
               
                 Q13361 
                 Microfibrillar-associated protein 5 
                 MFAP5 
               
               
                 Q13410 
                 Butyrophilin subfamily 1 member A1 
                 BTN1A1 
               
               
                 Q13421 
                 Mesothelin, cleaved form 
                 MSLN 
               
               
                 Q13429 
                 Insulin-like growth factor I 
                 IGF-I 
               
               
                 Q13443 
                 Disintegrin and metalloproteinase domain- 
                 ADAM9 
               
               
                   
                 containing protein 9 
               
               
                 Q13519 
                 Neuropeptide 1 
                 PNOC 
               
               
                 Q13751 
                 Laminin subunit beta-3 
                 LAMB3 
               
               
                 Q13753 
                 Laminin subunit gamma-2 
                 LAMC2 
               
               
                 Q13790 
                 Apolipoprotein F 
                 APOF 
               
               
                 Q13822 
                 Ectonucleotide 
                 ENPP2 
               
               
                   
                 pyrophosphatase/phosphodiesterase family 
               
               
                   
                 member 2 
               
               
                 Q14031 
                 Collagen alpha-6(IV) chain 
                 COL4A6 
               
               
                 Q14050 
                 Collagen alpha-3(IX) chain 
                 COL9A3 
               
               
                 Q14055 
                 Collagen alpha-2(IX) chain 
                 COL9A2 
               
               
                 Q14112 
                 Nidogen-2 
                 NID2 
               
               
                 Q14114 
                 Low-density lipoprotein receptor-related protein 8 
                 LRP8 
               
               
                 Q14118 
                 Dystroglycan 
                 DAG1 
               
               
                 Q14314 
                 Fibroleukin 
                 FGL2 
               
               
                 Q14393 
                 Growth arrest-specific protein 6 
                 GAS6 
               
               
                 Q14406 
                 Chorionic somatomammotropin hormone-like 1 
                 CSHL1 
               
               
                 Q14507 
                 Epididymal secretory protein E3-alpha 
                 EDDM3A 
               
               
                 Q14508 
                 WAP four-disulfide core domain protein 2 
                 WFDC2 
               
               
                 Q14512 
                 Fibroblast growth factor-binding protein 1 
                 FGFBP1 
               
               
                 Q14515 
                 SPARC-like protein 1 
                 SPARCL1 
               
               
                 Q14520 
                 Hyaluronan-binding protein 2 27 kDa light chain 
                 HABP2 
               
               
                 Q14563 
                 Semaphorin-3A 
                 SEMA3A 
               
               
                 Q14623 
                 Indian hedgehog protein 
                 IHH 
               
               
                 Q14624 
                 Inter-alpha-trypsin inhibitor heavy chain H4 
                 ITIH4 
               
               
                 Q14667 
                 UPF0378 protein KIAA0100 
                 KIAA0100 
               
               
                 Q14703 
                 Membrane-bound transcription factor site-1 
                 MBTPS1 
               
               
                   
                 protease 
               
               
                 Q14766 
                 Latent-transforming growth factor beta-binding 
                 LTBP1 
               
               
                   
                 protein 1 
               
               
                 Q14767 
                 Latent-transforming growth factor beta-binding 
                 LTBP2 
               
               
                   
                 protein 2 
               
               
                 Q14773 
                 Intercellular adhesion molecule 4 
                 ICAM4 
               
               
                 Q14993 
                 Collagen alpha-1(XIX) chain 
                 COL19A1 
               
               
                 Q14CN2 
                 Calcium-activated chloride channel regulator 4, 
                 CLCA4 
               
               
                   
                 110 kDa form 
               
               
                 Q15046 
                 Lysine--tRNA ligase 
                 KARS 
               
               
                 Q15063 
                 Periostin 
                 POSTN 
               
               
                 Q15109 
                 Advanced glycosylation end product-specific 
                 AGER 
               
               
                   
                 receptor 
               
               
                 Q15113 
                 Procollagen C-endopeptidase enhancer 1 
                 PCOLCE 
               
               
                 Q15166 
                 Serum paraoxonase/lactonase 3 
                 PON3 
               
               
                 Q15195 
                 Plasminogen-like protein A 
                 PLGLA 
               
               
                 Q15198 
                 Platelet-derived growth factor receptor-like protein 
                 PDGFRL 
               
               
                 Q15223 
                 Poliovirus receptor-related protein 1 
                 PVRL1 
               
               
                 Q15238 
                 Pregnancy-specific beta-1-glycoprotein 5 
                 PSG5 
               
               
                 Q15363 
                 Transmembrane emp24 domain-containing protein 2 
                 TMED2 
               
               
                 Q15375 
                 Ephrin type-A receptor 7 
                 EPHA7 
               
               
                 Q15389 
                 Angiopoietin-1 
                 ANGPT1 
               
               
                 Q15465 
                 Sonic hedgehog protein 
                 SHH 
               
               
                 Q15485 
                 Ficolin-2 
                 FCN2 
               
               
                 Q15517 
                 Corneodesmosin 
                 CDSN 
               
               
                 Q15582 
                 Transforming growth factor-beta-induced protein 
                 TGFBI 
               
               
                   
                 ig-h3 
               
               
                 Q15661 
                 Tryptase alpha/beta-1 
                 TPSAB1 
               
               
                 Q15726 
                 Metastin 
                 KISS1 
               
               
                 Q15782 
                 Chitinase-3-like protein 2 
                 CHI3L2 
               
               
                 Q15828 
                 Cystatin-M 
                 CST6 
               
               
                 Q15846 
                 Clusterin-like protein 1 
                 CLUL1 
               
               
                 Q15848 
                 Adiponectin 
                 ADIPOQ 
               
               
                 Q16206 
                 Protein disulfide-thiol oxidoreductase 
                 ENOX2 
               
               
                 Q16270 
                 Insulin-like growth factor-binding protein 7 
                 IGFBP7 
               
               
                 Q16363 
                 Laminin subunit alpha-4 
                 LAMA4 
               
               
                 Q16378 
                 Proline-rich protein 4 
                 PRR4 
               
               
                 Q16557 
                 Pregnancy-specific beta-1-glycoprotein 3 
                 PSG3 
               
               
                 Q16568 
                 CART(42-89) 
                 CARTPT 
               
               
                 Q16610 
                 Extracellular matrix protein 1 
                 ECM1 
               
               
                 Q16619 
                 Cardiotrophin-1 
                 CTF1 
               
               
                 Q16623 
                 Syntaxin-1A 
                 STX1A 
               
               
                 Q16627 
                 HCC-1(9-74) 
                 CCL14 
               
               
                 Q16651 
                 Prostasin light chain 
                 PRSS8 
               
               
                 Q16661 
                 Guanylate cyclase C-activating peptide 2 
                 GUCA2B 
               
               
                 Q16663 
                 CCL15(29-92) 
                 CCL15 
               
               
                 Q16674 
                 Melanoma-derived growth regulatory protein 
                 MIA 
               
               
                 Q16769 
                 Glutaminyl-peptide cyclotransferase 
                 QPCT 
               
               
                 Q16787 
                 Laminin subunit alpha-3 
                 LAMA3 
               
               
                 Q16842 
                 CMP-N-acetylneuraminate-beta-galactosamide- 
                 ST3GAL2 
               
               
                   
                 alpha-2,3-sialyltransferase 2 
               
               
                 Q17RR3 
                 Pancreatic lipase-related protein 3 
                 PNLIPRP3 
               
               
                 Q17RW2 
                 Collagen alpha-1(XXIV) chain 
                 COL24A1 
               
               
                 Q17RY6 
                 Lymphocyte antigen 6K 
                 LY6K 
               
               
                 Q1L6U9 
                 Prostate-associated microseminoprotein 
                 MSMP 
               
               
                 Q1W4C9 
                 Serine protease inhibitor Kazal-type 13 
                 SPINK13 
               
               
                 Q1ZYL8 
                 Izumo sperm-egg fusion protein 4 
                 IZUMO4 
               
               
                 Q29960 
                 HLA class I histocompatibility antigen, Cw-16 
                 HLA-C 
               
               
                   
                 alpha chain 
               
               
                 Q2I0M5 
                 R-spondin-4 
                 RSPO4 
               
               
                 Q2L4Q9 
                 Serine protease 53 
                 PRSS53 
               
               
                 Q2MKA7 
                 R-spondin-1 
                 RSPO1 
               
               
                 Q2MV58 
                 Tectonic-1 
                 TCTN1 
               
               
                 Q2TAL6 
                 Brorin 
                 VWC2 
               
               
                 Q2UY09 
                 Collagen alpha-1(XXVIII) chain 
                 COL28A1 
               
               
                 Q2VPA4 
                 Complement component receptor 1-like protein 
                 CR1L 
               
               
                 Q2WEN9 
                 Carcinoembryonic antigen-related cell adhesion 
                 CEACAM16 
               
               
                   
                 molecule 16 
               
               
                 Q30KP8 
                 Beta-defensin 136 
                 DEFB136 
               
               
                 Q30KP9 
                 Beta-defensin 135 
                 DEFB135 
               
               
                 Q30KQ1 
                 Beta-defensin 133 
                 DEFB133 
               
               
                 Q30KQ2 
                 Beta-defensin 130 
                 DEFB130 
               
               
                 Q30KQ4 
                 Beta-defensin 116 
                 DEFB116 
               
               
                 Q30KQ5 
                 Beta-defensin 115 
                 DEFB115 
               
               
                 Q30KQ6 
                 Beta-defensin 114 
                 DEFB114 
               
               
                 Q30KQ7 
                 Beta-defensin 113 
                 DEFB113 
               
               
                 Q30KQ8 
                 Beta-defensin 112 
                 DEFB112 
               
               
                 Q30KQ9 
                 Beta-defensin 110 
                 DEFB110 
               
               
                 Q30KR1 
                 Beta-defensin 109 
                 DEFB109P1 
               
               
                 Q32P28 
                 Prolyl 3-hydroxylase 1 
                 LEPRE1 
               
               
                 Q3B7J2 
                 Glucose-fructose oxidoreductase domain- 
                 GFOD2 
               
               
                   
                 containing protein 2 
               
               
                 Q3SY79 
                 Protein Wnt 
                 WNT3A 
               
               
                 Q3T906 
                 N-acetylglucosamine-1-phosphotransferase 
                 GNPTAB 
               
               
                   
                 subunits alpha/beta 
               
               
                 Q495T6 
                 Membrane metallo-endopeptidase-like 1 
                 MMEL1 
               
               
                 Q49AH0 
                 Cerebral dopamine neurotrophic factor 
                 CDNF 
               
               
                 Q4G0G5 
                 Secretoglobin family 2B member 2 
                 SCGB2B2 
               
               
                 Q4G0M1 
                 Protein FAM132B 
                 FAM132B 
               
               
                 Q4LDE5 
                 Sushi, von Willebrand factor type A, EGF and 
                 SVEP1 
               
               
                   
                 pentraxin domain-containing protein 1 
               
               
                 Q4QY38 
                 Beta-defensin 134 
                 DEFB134 
               
               
                 Q4VAJ4 
                 Protein Wnt 
                 WNT10B 
               
               
                 Q4W5P6 
                 Protein TMEM155 
                 TMEM155 
               
               
                 Q4ZHG4 
                 Fibronectin type III domain-containing protein 1 
                 FNDC1 
               
               
                 Q53H76 
                 Phospholipase A1 member A 
                 PLA1A 
               
               
                 Q53RD9 
                 Fibulin-7 
                 FBLN7 
               
               
                 Q53S33 
                 BolA-like protein 3 
                 BOLA3 
               
               
                 Q5BLP8 
                 Neuropeptide-like protein C4orf48 
                 C4orf48 
               
               
                 Q5DT21 
                 Serine protease inhibitor Kazal-type 9 
                 SPINK9 
               
               
                 Q5EBL8 
                 PDZ domain-containing protein 11 
                 PDZD11 
               
               
                 Q5FYB0 
                 Arylsulfatase J 
                 ARSJ 
               
               
                 Q5FYB1 
                 Arylsulfatase I 
                 ARSI 
               
               
                 Q5GAN3 
                 Ribonuclease-like protein 13 
                 RNASE13 
               
               
                 Q5GAN4 
                 Ribonuclease-like protein 12 
                 RNASE12 
               
               
                 Q5GAN6 
                 Ribonuclease-like protein 10 
                 RNASE10 
               
               
                 Q5GFL6 
                 von Willebrand factor A domain-containing 
                 VWA2 
               
               
                   
                 protein 2 
               
               
                 Q5H8A3 
                 Neuromedin-S 
                 NMS 
               
               
                 Q5H8C1 
                 FRAS1-related extracellular matrix protein 1 
                 FREM1 
               
               
                 Q5IJ48 
                 Protein crumbs homolog 2 
                 CRB2 
               
               
                 Q5J5C9 
                 Beta-defensin 121 
                 DEFB121 
               
               
                 Q5JS37 
                 NHL repeat-containing protein 3 
                 NHLRC3 
               
               
                 Q5JTB6 
                 Placenta-specific protein 9 
                 PLAC9 
               
               
                 Q5JU69 
                 Torsin-2A 
                 TOR2A 
               
               
                 Q5JXM2 
                 Methyltransferase-like protein 24 
                 METTL24 
               
               
                 Q5JZY3 
                 Ephrin type-A receptor 10 
                 EPHA10 
               
               
                 Q5K4E3 
                 Polyserase-2 
                 PRSS36 
               
               
                 Q5SRR4 
                 Lymphocyte antigen 6 complex locus protein G5c 
                 LY6G5C 
               
               
                 Q5T1H1 
                 Protein eyes shut homolog 
                 EYS 
               
               
                 Q5T4F7 
                 Secreted frizzled-related protein 5 
                 SFRP5 
               
               
                 Q5T4W7 
                 Artemin 
                 ARTN 
               
               
                 Q5T7M4 
                 Protein FAM132A 
                 FAM132A 
               
               
                 Q5TEH8 
                 Protein Wnt 
                 WNT2B 
               
               
                 Q5TIE3 
                 von Willebrand factor A domain-containing 
                 VWA5B1 
               
               
                   
                 protein 5B1 
               
               
                 Q5UCC4 
                 ER membrane protein complex subunit 10 
                 EMC10 
               
               
                 Q5VST6 
                 Abhydrolase domain-containing protein 
                 FAM108B1 
               
               
                   
                 FAM108B1 
               
               
                 Q5VTL7 
                 Fibronectin type III domain-containing protein 7 
                 FNDC7 
               
               
                 Q5VUM1 
                 UPF0369 protein C6orf57 
                 C6orf57 
               
               
                 Q5VV43 
                 Dyslexia-associated protein KIAA0319 
                 KIAA0319 
               
               
                 Q5VWW1 
                 Complement C1q-like protein 3 
                 C1QL3 
               
               
                 Q5VXI9 
                 Lipase member N 
                 LIPN 
               
               
                 Q5VXJ0 
                 Lipase member K 
                 LIPK 
               
               
                 Q5VXM1 
                 CUB domain-containing protein 2 
                 CDCP2 
               
               
                 Q5VYX0 
                 Renalase 
                 RNLS 
               
               
                 Q5VYY2 
                 Lipase member M 
                 LIPM 
               
               
                 Q5W186 
                 Cystatin-9 
                 CST9 
               
               
                 Q5W5W9 
                 Regulated endocrine-specific protein 18 
                 RESP18 
               
               
                 Q5XG92 
                 Carboxylesterase 4A 
                 CES4A 
               
               
                 Q63HQ2 
                 Pikachurin 
                 EGFLAM 
               
               
                 Q641Q3 
                 Meteorin-like protein 
                 METRNL 
               
               
                 Q66K79 
                 Carboxypeptidase Z 
                 CPZ 
               
               
                 Q685J3 
                 Mucin-17 
                 MUC17 
               
               
                 Q68BL7 
                 Olfactomedin-like protein 2A 
                 OLFML2A 
               
               
                 Q68BL8 
                 Olfactomedin-like protein 2B 
                 OLFML2B 
               
               
                 Q68DV7 
                 E3 ubiquitin-protein ligase RNF43 
                 RNF43 
               
               
                 Q6B9Z1 
                 Insulin growth factor-like family member 4 
                 IGFL4 
               
               
                 Q6BAA4 
                 Fc receptor-like B 
                 FCRLB 
               
               
                 Q6E0U4 
                 Dermokine 
                 DMKN 
               
               
                 Q6EMK4 
                 Vasorin 
                 VASN 
               
               
                 Q6FHJ7 
                 Secreted frizzled-related protein 4 
                 SFRP4 
               
               
                 Q6GPI1 
                 Chymotrypsin B2 chain B 
                 CTRB2 
               
               
                 Q6GTS8 
                 Probable Carboxypeptidase PM20D1 
                 PM20D1 
               
               
                 Q6H9L7 
                 Isthmin-2 
                 ISM2 
               
               
                 Q6IE36 
                 Ovostatin homolog 2 
                 OVOS2 
               
               
                 Q6IE37 
                 Ovostatin homolog 1 
                 OVOS1 
               
               
                 Q6IE38 
                 Serine protease inhibitor Kazal-type 14 
                 SPINK14 
               
               
                 Q6ISS4 
                 Leukocyte-associated immunoglobulin-like 
                 LAIR2 
               
               
                   
                 receptor 2 
               
               
                 Q6JVE5 
                 Epididymal-specific lipocalin-12 
                 LCN12 
               
               
                 Q6JVE6 
                 Epididymal-specific lipocalin-10 
                 LCN10 
               
               
                 Q6JVE9 
                 Epididymal-specific lipocalin-8 
                 LCN8 
               
               
                 Q6KF10 
                 Growth/differentiation factor 6 
                 GDF6 
               
               
                 Q6MZW2 
                 Follistatin-related protein 4 
                 FSTL4 
               
               
                 Q6NSX1 
                 Coiled-coil domain-containing protein 70 
                 CCDC70 
               
               
                 Q6NT32 
                 Carboxylesterase 5A 
                 CES5A 
               
               
                 Q6NT52 
                 Choriogonadotropin subunit beta variant 2 
                 CGB2 
               
               
                 Q6NUI6 
                 Chondroactherin-like protein 
                 CHADL 
               
               
                 Q6NUJ1 
                 Saposin A-like 
                 PSAPL1 
               
               
                 Q6P093 
                 Arylacetamide deacetylase-like 2 
                 AADACL2 
               
               
                 Q6P4A8 
                 Phospholipase B-like 1 
                 PLBD1 
               
               
                 Q6P5S2 
                 UPF0762 protein C6orf58 
                 C6orf58 
               
               
                 Q6P988 
                 Protein notum homolog 
                 NOTUM 
               
               
                 Q6PCB0 
                 von Willebrand factor A domain-containing 
                 VWA1 
               
               
                   
                 protein 1 
               
               
                 Q6PDA7 
                 Sperm-associated antigen 11A 
                 SPAG11A 
               
               
                 Q6PEW0 
                 Inactive serine protease 54 
                 PRSS54 
               
               
                 Q6PEZ8 
                 Podocan-like protein 1 
                 PODNL1 
               
               
                 Q6PKH6 
                 Dehydrogenase/reductase SDR family member 4- 
                 DHRS4L2 
               
               
                   
                 like 2 
               
               
                 Q6Q788 
                 Apolipoprotein A-V 
                 APOA5 
               
               
                 Q6SPF0 
                 Atherin 
                 SAMD1 
               
               
                 Q6UDR6 
                 Kunitz-type protease inhibitor 4 
                 SPINT4 
               
               
                 Q6URK8 
                 Testis, prostate and placenta-expressed protein 
                 TEPP 
               
               
                 Q6UW01 
                 Cerebellin-3 
                 CBLN3 
               
               
                 Q6UW10 
                 Surfactant-associated protein 2 
                 SFTA2 
               
               
                 Q6UW15 
                 Regenerating islet-derived protein 3-gamma 
                 REG3G 
               
               
                 Q6UW32 
                 Insulin growth factor-like family member 1 
                 IGFL1 
               
               
                 Q6UW78 
                 UPF0723 protein C11orf83 
                 C11orf83 
               
               
                 Q6UW88 
                 Epigen 
                 EPGN 
               
               
                 Q6UWE3 
                 Colipase-like protein 2 
                 CLPSL2 
               
               
                 Q6UWF7 
                 NXPE family member 4 
                 NXPE4 
               
               
                 Q6UWF9 
                 Protein FAM180A 
                 FAM180A 
               
               
                 Q6UWM5 
                 GLIPR1-like protein 1 
                 GLIPR1L1 
               
               
                 Q6UWN8 
                 Serine protease inhibitor Kazal-type 6 
                 SPINK6 
               
               
                 Q6UWP2 
                 Dehydrogenase/reductase SDR family member 11 
                 DHRS11 
               
               
                 Q6UWP8 
                 Suprabasin 
                 SBSN 
               
               
                 Q6UWQ5 
                 Lysozyme-like protein 1 
                 LYZL1 
               
               
                 Q6UWQ7 
                 Insulin growth factor-like family member 2 
                 IGFL2 
               
               
                 Q6UWR7 
                 Ectonucleotide 
                 ENPP6 
               
               
                   
                 pyrophosphatase/phosphodiesterase family 
               
               
                   
                 member 6 soluble form 
               
               
                 Q6UWT2 
                 Adropin 
                 ENHO 
               
               
                 Q6UWU2 
                 Beta-galactosidase-1-like protein 
                 GLB1L 
               
               
                 Q6UWW0 
                 Lipocalin-15 
                 LCN15 
               
               
                 Q6UWX4 
                 HHIP-like protein 2 
                 HHIPL2 
               
               
                 Q6UWY0 
                 Arylsulfatase K 
                 ARSK 
               
               
                 Q6UWY2 
                 Serine protease 57 
                 PRSS57 
               
               
                 Q6UWY5 
                 Olfactomedin-like protein 1 
                 OLFML1 
               
               
                 Q6UX06 
                 Olfactomedin-4 
                 OLFM4 
               
               
                 Q6UX07 
                 Dehydrogenase/reductase SDR family member 13 
                 DHRS13 
               
               
                 Q6UX39 
                 Amelotin 
                 AMTN 
               
               
                 Q6UX46 
                 Protein FAM150B 
                 FAM150B 
               
               
                 Q6UX73 
                 UPF0764 protein C16orf89 
                 C16orf89 
               
               
                 Q6UXB0 
                 Protein FAM131A 
                 FAM131A 
               
               
                 Q6UXB1 
                 Insulin growth factor-like family member 3 
                 IGFL3 
               
               
                 Q6UXB2 
                 VEGF co-regulated chemokine 1 
                 CXCL17 
               
               
                 Q6UXF7 
                 C-type lectin domain family 18 member B 
                 CLEC18B 
               
               
                 Q6UXH0 
                 Hepatocellular carcinoma-associated protein TD26 
                 C19orf80 
               
               
                 Q6UXH1 
                 Cysteine-rich with EGF-like domain protein 2 
                 CRELD2 
               
               
                 Q6UXH8 
                 Collagen and calcium-binding EGF domain- 
                 CCBE1 
               
               
                   
                 containing protein 1 
               
               
                 Q6UXH9 
                 Inactive serine protease PAMR1 
                 PAMR1 
               
               
                 Q6UXI7 
                 Vitrin 
                 VIT 
               
               
                 Q6UXI9 
                 Nephronectin 
                 NPNT 
               
               
                 Q6UXN2 
                 Trem-like transcript 4 protein 
                 TREML4 
               
               
                 Q6UXS0 
                 C-type lectin domain family 19 member A 
                 CLEC19A 
               
               
                 Q6UXT8 
                 Protein FAM150A 
                 FAM150A 
               
               
                 Q6UXT9 
                 Abhydrolase domain-containing protein 15 
                 ABHD15 
               
               
                 Q6UXV4 
                 Apolipoprotein O-like 
                 APOOL 
               
               
                 Q6UXX5 
                 Inter-alpha-trypsin inhibitor heavy chain H6 
                 ITIH6 
               
               
                 Q6UXX9 
                 R-spondin-2 
                 RSPO2 
               
               
                 Q6UY14 
                 ADAMTS-like protein 4 
                 ADAMTSL4 
               
               
                 Q6UY27 
                 Prostate and testis expressed protein 2 
                 PATE2 
               
               
                 Q6W4X9 
                 Mucin-6 
                 MUC6 
               
               
                 Q6WN34 
                 Chordin-like protein 2 
                 CHRDL2 
               
               
                 Q6WRI0 
                 Immunoglobulin superfamily member 10 
                 IGSF10 
               
               
                 Q6X4U4 
                 Sclerostin domain-containing protein 1 
                 SOSTDC1 
               
               
                 Q6X784 
                 Zona pellucida-binding protein 2 
                 ZPBP2 
               
               
                 Q6XE38 
                 Secretoglobin family 1D member 4 
                 SCGB1D4 
               
               
                 Q6XPR3 
                 Repetin 
                 RPTN 
               
               
                 Q6XZB0 
                 Lipase member I 
                 LIPI 
               
               
                 Q6ZMM2 
                 ADAMTS-like protein 5 
                 ADAMTSL5 
               
               
                 Q6ZMP0 
                 Thrombospondin type-1 domain-containing 
                 THSD4 
               
               
                   
                 protein 4 
               
               
                 Q6ZNF0 
                 Iron/zinc purple acid phosphatase-like protein 
                 PAPL 
               
               
                 Q6ZRI0 
                 Otogelin 
                 OTOG 
               
               
                 Q6ZRP7 
                 Sulfhydryl oxidase 2 
                 QSOX2 
               
               
                 Q6ZWJ8 
                 Kielin/chordin-like protein 
                 KCP 
               
               
                 Q75N90 
                 Fibrillin-3 
                 FBN3 
               
               
                 Q765I0 
                 Urotensin-2B 
                 UTS2D 
               
               
                 Q76B58 
                 Protein FAM5C 
                 FAM5C 
               
               
                 Q76LX8 
                 A disintegrin and metalloproteinase with 
                 ADAMTS13 
               
               
                   
                 thrombospondin motifs 13 
               
               
                 Q76M96 
                 Coiled-coil domain-containing protein 80 
                 CCDC80 
               
               
                 Q7L1S5 
                 Carbohydrate sulfotransferase 9 
                 CHST9 
               
               
                 Q7L513 
                 Fc receptor-like A 
                 FCRLA 
               
               
                 Q7L8A9 
                 Vasohibin-1 
                 VASH1 
               
               
                 Q7RTM1 
                 Otopetrin-1 
                 OTOP1 
               
               
                 Q7RTW8 
                 Otoancorin 
                 OTOA 
               
               
                 Q7RTY5 
                 Serine protease 48 
                 PRSS48 
               
               
                 Q7RTY7 
                 Ovochymase-1 
                 OVCH1 
               
               
                 Q7RTZ1 
                 Ovochymase-2 
                 OVCH2 
               
               
                 Q7Z304 
                 MAM domain-containing protein 2 
                 MAMDC2 
               
               
                 Q7Z3S9 
                 Notch homolog 2 N-terminal-like protein 
                 NOTCH2NL 
               
               
                 Q7Z4H4 
                 Intermedin-short 
                 ADM2 
               
               
                 Q7Z4P5 
                 Growth/differentiation factor 7 
                 GDF7 
               
               
                 Q7Z4R8 
                 UPF0669 protein C6orf120 
                 C6orf120 
               
               
                 Q7Z4W2 
                 Lysozyme-like protein 2 
                 LYZL2 
               
               
                 Q7Z5A4 
                 Serine protease 42 
                 PRSS42 
               
               
                 Q7Z5A7 
                 Protein FAM19A5 
                 FAM19A5 
               
               
                 Q7Z5A8 
                 Protein FAM19A3 
                 FAM19A3 
               
               
                 Q7Z5A9 
                 Protein FAM19A1 
                 FAM19A1 
               
               
                 Q7Z5J1 
                 Hydroxysteroid 11-beta-dehydrogenase 1-like 
                 HSD11B1L 
               
               
                   
                 protein 
               
               
                 Q7Z5L0 
                 Vitelline membrane outer layer protein 1 homolog 
                 VMO1 
               
               
                 Q7Z5L3 
                 Complement C1q-like protein 2 
                 C1QL2 
               
               
                 Q7Z5L7 
                 Podocan 
                 PODN 
               
               
                 Q7Z5P4 
                 17-beta-hydroxysteroid dehydrogenase 13 
                 HSD17B13 
               
               
                 Q7Z5P9 
                 Mucin-19 
                 MUC19 
               
               
                 Q7Z5Y6 
                 Bone morphogenetic protein 8A 
                 BMP8A 
               
               
                 Q7Z7B7 
                 Beta-defensin 132 
                 DEFB132 
               
               
                 Q7Z7B8 
                 Beta-defensin 128 
                 DEFB128 
               
               
                 Q7Z7C8 
                 Transcription initiation factor TFIID subunit 8 
                 TAF8 
               
               
                 Q7Z7H5 
                 Transmembrane emp24 domain-containing protein 4 
                 TMED4 
               
               
                 Q86SG7 
                 Lysozyme g-like protein 2 
                 LYG2 
               
               
                 Q86SI9 
                 Protein CEI 
                 C5orf38 
               
               
                 Q86TE4 
                 Leucine zipper protein 2 
                 LUZP2 
               
               
                 Q86TH1 
                 ADAMTS-like protein 2 
                 ADAMTSL2 
               
               
                 Q86U17 
                 Serpin A11 
                 SERPINA11 
               
               
                 Q86UU9 
                 Endokinin-A 
                 TAC4 
               
               
                 Q86UW8 
                 Hyaluronan and proteoglycan link protein 4 
                 HAPLN4 
               
               
                 Q86UX2 
                 Inter-alpha-trypsin inhibitor heavy chain H5 
                 ITIH5 
               
               
                 Q86V24 
                 Adiponectin receptor protein 2 
                 ADIPOR2 
               
               
                 Q86VB7 
                 Soluble CD163 
                 CD163 
               
               
                 Q86VR8 
                 Four-jointed box protein 1 
                 FJX1 
               
               
                 Q86WD7 
                 Serpin A9 
                 SERPINA9 
               
               
                 Q86WN2 
                 Interferon epsilon 
                 IFNE 
               
               
                 Q86WS3 
                 Placenta-specific 1-like protein 
                 PLAC1L 
               
               
                 Q86X52 
                 Chondroitin sulfate synthase 1 
                 CHSY1 
               
               
                 Q86XP6 
                 Gastrokine-2 
                 GKN2 
               
               
                 Q86XS5 
                 Angiopoietin-related protein 5 
                 ANGPTL5 
               
               
                 Q86Y27 
                 B melanoma antigen 5 
                 BAGE5 
               
               
                 Q86Y28 
                 B melanoma antigen 4 
                 BAGE4 
               
               
                 Q86Y29 
                 B melanoma antigen 3 
                 BAGE3 
               
               
                 Q86Y30 
                 B melanoma antigen 2 
                 BAGE2 
               
               
                 Q86Y38 
                 Xylosyltransferase 1 
                 XYLT1 
               
               
                 Q86Y78 
                 Ly6/PLAUR domain-containing protein 6 
                 LYPD6 
               
               
                 Q86YD3 
                 Transmembrane protein 25 
                 TMEM25 
               
               
                 Q86YJ6 
                 Threonine synthase-like 2 
                 THNSL2 
               
               
                 Q86YW7 
                 Glycoprotein hormone beta-5 
                 GPHB5 
               
               
                 Q86Z23 
                 Complement C1q-like protein 4 
                 C1QL4 
               
               
                 Q8IU57 
                 Interleukin-28 receptor subunit alpha 
                 IL28RA 
               
               
                 Q8IUA0 
                 WAP four-disulfide core domain protein 8 
                 WFDC8 
               
               
                 Q8IUB2 
                 WAP four-disulfide core domain protein 3 
                 WFDC3 
               
               
                 Q8IUB3 
                 Protein WFDC10B 
                 WFDC10B 
               
               
                 Q8IUB5 
                 WAP four-disulfide core domain protein 13 
                 WFDC13 
               
               
                 Q8IUH2 
                 Protein CREG2 
                 CREG2 
               
               
                 Q8IUK5 
                 Plexin domain-containing protein 1 
                 PLXDC1 
               
               
                 Q8IUL8 
                 Cartilage intermediate layer protein 2 C2 
                 CILP2 
               
               
                 Q8IUX7 
                 Adipocyte enhancer-binding protein 1 
                 AEBP1 
               
               
                 Q8IUX8 
                 Epidermal growth factor-like protein 6 
                 EGFL6 
               
               
                 Q8IVL8 
                 Carboxypeptidase O 
                 CPO 
               
               
                 Q8IVN8 
                 Somatomedin-B and thrombospondin type-1 
                 SBSPON 
               
               
                   
                 domain-containing protein 
               
               
                 Q8IVW8 
                 Protein spinster homolog 2 
                 SPNS2 
               
               
                 Q8IW75 
                 Serpin A12 
                 SERPINA12 
               
               
                 Q8IW92 
                 Beta-galactosidase-1-like protein 2 
                 GLB1L2 
               
               
                 Q8IWL1 
                 Pulmonary surfactant-associated protein A2 
                 SFTPA2 
               
               
                 Q8IWL2 
                 Pulmonary surfactant-associated protein A1 
                 SFTPA1 
               
               
                 Q8IWV2 
                 Contactin-4 
                 CNTN4 
               
               
                 Q8IWY4 
                 Signal peptide, CUB and EGF-like domain- 
                 SCUBE1 
               
               
                   
                 containing protein 1 
               
               
                 Q8IX30 
                 Signal peptide, CUB and EGF-like domain- 
                 SCUBE3 
               
               
                   
                 containing protein 3 
               
               
                 Q8IXA5 
                 Sperm acrosome membrane-associated protein 3, 
                 SPACA3 
               
               
                   
                 membrane form 
               
               
                 Q8IXB1 
                 DnaJ homolog subfamily C member 10 
                 DNAJC10 
               
               
                 Q8IXL6 
                 Extracellular serine/threonine protein kinase 
                 FAM20C 
               
               
                   
                 Fam20C 
               
               
                 Q8IYD9 
                 Lung adenoma susceptibility protein 2 
                 LAS2 
               
               
                 Q8IYP2 
                 Serine protease 58 
                 PRSS58 
               
               
                 Q8IYS5 
                 Osteoclast-associated immunoglobulin-like 
                 OSCAR 
               
               
                   
                 receptor 
               
               
                 Q8IZC6 
                 Collagen alpha-1(XXVII) chain 
                 COL27A1 
               
               
                 Q8IZJ3 
                 C3 and PZP-like alpha-2-macroglobulin domain- 
                 CPAMD8 
               
               
                   
                 containing protein 8 
               
               
                 Q8IZN7 
                 Beta-defensin 107 
                 DEFB107B 
               
               
                 Q8N0V4 
                 Leucine-rich repeat LGI family member 2 
                 LGI2 
               
               
                 Q8N104 
                 Beta-defensin 106 
                 DEFB106B 
               
               
                 Q8N119 
                 Matrix metalloproteinase-21 
                 MMP21 
               
               
                 Q8N129 
                 Protein canopy homolog 4 
                 CNPY4 
               
               
                 Q8N135 
                 Leucine-rich repeat LGI family member 4 
                 LGI4 
               
               
                 Q8N145 
                 Leucine-rich repeat LGI family member 3 
                 LGI3 
               
               
                 Q8N158 
                 Glypican-2 
                 GPC2 
               
               
                 Q8N1E2 
                 Lysozyme g-like protein 1 
                 LYG1 
               
               
                 Q8N2E2 
                 von Willebrand factor D and EGF domain- 
                 VWDE 
               
               
                   
                 containing protein 
               
               
                 Q8N2E6 
                 Prosalusin 
                 TOR2A 
               
               
                 Q8N2S1 
                 Latent-transforming growth factor beta-binding 
                 LTBP4 
               
               
                   
                 protein 4 
               
               
                 Q8N302 
                 Angiogenic factor with G patch and FHA domains 1 
                 AGGF1 
               
               
                 Q8N307 
                 Mucin-20 
                 MUC20 
               
               
                 Q8N323 
                 NXPE family member 1 
                 NXPE1 
               
               
                 Q8N387 
                 Mucin-15 
                 MUC15 
               
               
                 Q8N3Z0 
                 Inactive serine protease 35 
                 PRSS35 
               
               
                 Q8N436 
                 Inactive carboxypeptidase-like protein X2 
                 CPXM2 
               
               
                 Q8N474 
                 Secreted frizzled-related protein 1 
                 SFRP1 
               
               
                 Q8N475 
                 Follistatin-related protein 5 
                 FSTL5 
               
               
                 Q8N4F0 
                 BPI fold-containing family B member 2 
                 BPIFB2 
               
               
                 Q8N4T0 
                 Carboxypeptidase A6 
                 CPA6 
               
               
                 Q8N5W8 
                 Protein FAM24B 
                 FAM24B 
               
               
                 Q8N687 
                 Beta-defensin 125 
                 DEFB125 
               
               
                 Q8N688 
                 Beta-defensin 123 
                 DEFB123 
               
               
                 Q8N690 
                 Beta-defensin 119 
                 DEFB119 
               
               
                 Q8N6C5 
                 Immunoglobulin superfamily member 1 
                 IGSF1 
               
               
                 Q8N6C8 
                 Leukocyte immunoglobulin-like receptor 
                 LILRA3 
               
               
                   
                 subfamily A member 3 
               
               
                 Q8N6G6 
                 ADAMTS-like protein 1 
                 ADAMTSL1 
               
               
                 Q8N6Y2 
                 Leucine-rich repeat-containing protein 17 
                 LRRC17 
               
               
                 Q8N729 
                 Neuropeptide W-23 
                 NPW 
               
               
                 Q8N8U9 
                 BMP-binding endothelial regulator protein 
                 BMPER 
               
               
                 Q8N907 
                 DAN domain family member 5 
                 DAND5 
               
               
                 Q8NAT1 
                 Glycosyltransferase-like domain-containing 
                 GTDC2 
               
               
                   
                 protein 2 
               
               
                 Q8NAU1 
                 Fibronectin type III domain-containing protein 5 
                 FNDC5 
               
               
                 Q8NB37 
                 Parkinson disease 7 domain-containing protein 1 
                 PDDC1 
               
               
                 Q8NBI3 
                 Draxin 
                 DRAXIN 
               
               
                 Q8NBM8 
                 Prenylcysteine oxidase-like 
                 PCYOX1L 
               
               
                 Q8NBP7 
                 Proprotein convertase subtilisin/kexin type 9 
                 PCSK9 
               
               
                 Q8NBQ5 
                 Estradiol 17-beta-dehydrogenase 11 
                 HSD17B11 
               
               
                 Q8NBV8 
                 Synaptotagmin-8 
                 SYT8 
               
               
                 Q8NCC3 
                 Group XV phospholipase A2 
                 PLA2G15 
               
               
                 Q8NCF0 
                 C-type lectin domain family 18 member C 
                 CLEC18C 
               
               
                 Q8NCW5 
                 NAD(P)H-hydrate epimerase 
                 APOA1BP 
               
               
                 Q8NDA2 
                 Hemicentin-2 
                 HMCN2 
               
               
                 Q8NDX9 
                 Lymphocyte antigen 6 complex locus protein G5b 
                 LY6G5B 
               
               
                 Q8NDZ4 
                 Deleted in autism protein 1 
                 C3orf58 
               
               
                 Q8NEB7 
                 Acrosin-binding protein 
                 ACRBP 
               
               
                 Q8NES8 
                 Beta-defensin 124 
                 DEFB124 
               
               
                 Q8NET1 
                 Beta-defensin 108B 
                 DEFB108B 
               
               
                 Q8NEX5 
                 Protein WFDC9 
                 WFDC9 
               
               
                 Q8NEX6 
                 Protein WFDC11 
                 WFDC11 
               
               
                 Q8NF86 
                 Serine protease 33 
                 PRSS33 
               
               
                 Q8NFM7 
                 Interleukin-17 receptor D 
                 IL17RD 
               
               
                 Q8NFQ5 
                 BPI fold-containing family B member 6 
                 BPIFB6 
               
               
                 Q8NFQ6 
                 BPI fold-containing family C protein 
                 BPIFC 
               
               
                 Q8NFU4 
                 Follicular dendritic cell secreted peptide 
                 FDCSP 
               
               
                 Q8NFW1 
                 Collagen alpha-1(XXII) chain 
                 COL22A1 
               
               
                 Q8NG35 
                 Beta-defensin 105 
                 DEFB105B 
               
               
                 Q8NG41 
                 Neuropeptide B-23 
                 NPB 
               
               
                 Q8NHW6 
                 Otospiralin 
                 OTOS 
               
               
                 Q8NI99 
                 Angiopoietin-related protein 6 
                 ANGPTL6 
               
               
                 Q8TAA1 
                 Probable ribonuclease 11 
                 RNASE11 
               
               
                 Q8TAG5 
                 V-set and transmembrane domain-containing 
                 VSTM2A 
               
               
                   
                 protein 2A 
               
               
                 Q8TAL6 
                 Fin bud initiation factor homolog 
                 FIBIN 
               
               
                 Q8TAT2 
                 Fibroblast growth factor-binding protein 3 
                 FGFBP3 
               
               
                 Q8TAX7 
                 Mucin-7 
                 MUC7 
               
               
                 Q8TB22 
                 Spermatogenesis-associated protein 20 
                 SPATA20 
               
               
                 Q8TB73 
                 Protein NDNF 
                 NDNF 
               
               
                 Q8TB96 
                 T-cell immunomodulatory protein 
                 ITFG1 
               
               
                 Q8TC92 
                 Protein disulfide-thiol oxidoreductase 
                 ENOX1 
               
               
                 Q8TCV5 
                 WAP four-disulfide core domain protein 5 
                 WFDC5 
               
               
                 Q8TD06 
                 Anterior gradient protein 3 homolog 
                 AGR3 
               
               
                 Q8TD33 
                 Secretoglobin family 1C member 1 
                 SCGB1C1 
               
               
                 Q8TD46 
                 Cell surface glycoprotein CD200 receptor 1 
                 CD200R1 
               
               
                 Q8TDE3 
                 Ribonuclease 8 
                 RNASE8 
               
               
                 Q8TDF5 
                 Neuropilin and tolloid-like protein 1 
                 NETO1 
               
               
                 Q8TDL5 
                 BPI fold-containing family B member 1 
                 BPIFB1 
               
               
                 Q8TE56 
                 A disintegrin and metalloproteinase with 
                 ADAMTS17 
               
               
                   
                 thrombospondin motifs 17 
               
               
                 Q8TE57 
                 A disintegrin and metalloproteinase with 
                 ADAMTS16 
               
               
                   
                 thrombospondin motifs 16 
               
               
                 Q8TE58 
                 A disintegrin and metalloproteinase with 
                 ADAMTS15 
               
               
                   
                 thrombospondin motifs 15 
               
               
                 Q8TE59 
                 A disintegrin and metalloproteinase with 
                 ADAMTS19 
               
               
                   
                 thrombospondin motifs 19 
               
               
                 Q8TE60 
                 A disintegrin and metalloproteinase with 
                 ADAMTS18 
               
               
                   
                 thrombospondin motifs 18 
               
               
                 Q8TE99 
                 Acid phosphatase-like protein 2 
                 ACPL2 
               
               
                 Q8TER0 
                 Sushi, nidogen and EGF-like domain-containing 
                 SNED1 
               
               
                   
                 protein 1 
               
               
                 Q8TEU8 
                 WAP, kazal, immunoglobulin, kunitz and NTR 
                 WFIKKN2 
               
               
                   
                 domain-containing protein 2 
               
               
                 Q8WTQ1 
                 Beta-defensin 104 
                 DEFB104B 
               
               
                 Q8WTR8 
                 Netrin-5 
                 NTN5 
               
               
                 Q8WTU2 
                 Scavenger receptor cysteine-rich domain- 
                 SRCRB4D 
               
               
                   
                 containing group B protein 
               
               
                 Q8WU66 
                 Protein TSPEAR 
                 TSPEAR 
               
               
                 Q8WUA8 
                 Tsukushin 
                 TSKU 
               
               
                 Q8WUF8 
                 Protein FAM172A 
                 FAM172A 
               
               
                 Q8WUJ1 
                 Neuferricin 
                 CYB5D2 
               
               
                 Q8WUY1 
                 UPF0670 protein THEM6 
                 THEM6 
               
               
                 Q8WVN6 
                 Secreted and transmembrane protein 1 
                 SECTM1 
               
               
                 Q8WVQ1 
                 Soluble calcium-activated nucleotidase 1 
                 CANT1 
               
               
                 Q8WWA0 
                 Intelectin-1 
                 ITLN1 
               
               
                 Q8WWG1 
                 Neuregulin-4 
                 NRG4 
               
               
                 Q8WWQ2 
                 Inactive heparanase-2 
                 HPSE2 
               
               
                 Q8WWU7 
                 Intelectin-2 
                 ITLN2 
               
               
                 Q8WWY7 
                 WAP four-disulfide core domain protein 12 
                 WFDC12 
               
               
                 Q8WWY8 
                 Lipase member H 
                 LIPH 
               
               
                 Q8WWZ8 
                 Oncoprotein-induced transcript 3 protein 
                 OIT3 
               
               
                 Q8WX39 
                 Epididymal-specific lipocalin-9 
                 LCN9 
               
               
                 Q8WXA2 
                 Prostate and testis expressed protein 1 
                 PATE1 
               
               
                 Q8WXD2 
                 Secretogranin-3 
                 SCG3 
               
               
                 Q8WXF3 
                 Relaxin-3 A chain 
                 RLN3 
               
               
                 Q8WXI7 
                 Mucin-16 
                 MUC16 
               
               
                 Q8WXQ8 
                 Carboxypeptidase A5 
                 CPA5 
               
               
                 Q8WXS8 
                 A disintegrin and metalloproteinase with 
                 ADAMTS14 
               
               
                   
                 thrombospondin motifs 14 
               
               
                 Q92484 
                 Acid sphingomyelinase-like phosphodiesterase 3a 
                 SMPDL3A 
               
               
                 Q92485 
                 Acid sphingomyelinase-like phosphodiesterase 3b 
                 SMPDL3B 
               
               
                 Q92496 
                 Complement factor H-related protein 4 
                 CFHR4 
               
               
                 Q92520 
                 Protein FAM3C 
                 FAM3C 
               
               
                 Q92563 
                 Testican-2 
                 SPOCK2 
               
               
                 Q92583 
                 C-C motif chemokine 17 
                 CCL17 
               
               
                 Q92626 
                 Peroxidasin homolog 
                 PXDN 
               
               
                 Q92743 
                 Serine protease HTRA1 
                 HTRA1 
               
               
                 Q92752 
                 Tenascin-R 
                 TNR 
               
               
                 Q92765 
                 Secreted frizzled-related protein 3 
                 FRZB 
               
               
                 Q92819 
                 Hyaluronan synthase 2 
                 HAS2 
               
               
                 Q92820 
                 Gamma-glutamyl hydrolase 
                 GGH 
               
               
                 Q92824 
                 Proprotein convertase subtilisin/kexin type 5 
                 PCSK5 
               
               
                 Q92832 
                 Protein kinase C-binding protein NELL1 
                 NELL1 
               
               
                 Q92838 
                 Ectodysplasin-A, membrane form 
                 EDA 
               
               
                 Q92874 
                 Deoxyribonuclease-1-like 2 
                 DNASE1L2 
               
               
                 Q92876 
                 Kallikrein-6 
                 KLK6 
               
               
                 Q92913 
                 Fibroblast growth factor 13 
                 FGF13 
               
               
                 Q92954 
                 Proteoglycan 4 C-terminal part 
                 PRG4 
               
               
                 Q93038 
                 Tumor necrosis factor receptor superfamily 
                 TNFRSF25 
               
               
                   
                 member 25 
               
               
                 Q93091 
                 Ribonuclease K6 
                 RNASE6 
               
               
                 Q93097 
                 Protein Wnt-2b 
                 WNT2B 
               
               
                 Q93098 
                 Protein Wnt-8b 
                 WNT8B 
               
               
                 Q95460 
                 Major histocompatibility complex class I-related 
                 MR1 
               
               
                   
                 gene protein 
               
               
                 Q969D9 
                 Thymic stromal lymphopoietin 
                 TSLP 
               
               
                 Q969E1 
                 Liver-expressed antimicrobial peptide 2 
                 LEAP2 
               
               
                 Q969H8 
                 UPF0556 protein C19orf10 
                 C19orf10 
               
               
                 Q969Y0 
                 NXPE family member 3 
                 NXPE3 
               
               
                 Q96A54 
                 Adiponectin receptor protein 1 
                 ADIPOR1 
               
               
                 Q96A83 
                 Collagen alpha-1(XXVI) chain 
                 EMID2 
               
               
                 Q96A84 
                 EMI domain-containing protein 1 
                 EMID1 
               
               
                 Q96A98 
                 Tuberoinfundibular peptide of 39 residues 
                 PTH2 
               
               
                 Q96A99 
                 Pentraxin-4 
                 PTX4 
               
               
                 Q96BH3 
                 Epididymal sperm-binding protein 1 
                 ELSPBP1 
               
               
                 Q96BQ1 
                 Protein FAM3D 
                 FAM3D 
               
               
                 Q96CG8 
                 Collagen triple helix repeat-containing protein 1 
                 CTHRC1 
               
               
                 Q96DA0 
                 Zymogen granule protein 16 homolog B 
                 ZG16B 
               
               
                 Q96DN2 
                 von Willebrand factor C and EGF domain- 
                 VWCE 
               
               
                   
                 containing protein 
               
               
                 Q96DR5 
                 BPI fold-containing family A member 2 
                 BPIFA2 
               
               
                 Q96DR8 
                 Mucin-like protein 1 
                 MUCL1 
               
               
                 Q96DX4 
                 RING finger and SPRY domain-containing protein 1 
                 RSPRY1 
               
               
                 Q96EE4 
                 Coiled-coil domain-containing protein 126 
                 CCDC126 
               
               
                 Q96GS6 
                 Abhydrolase domain-containing protein 
                 FAM108A1 
               
               
                   
                 FAM108A1 
               
               
                 Q96GW7 
                 Brevican core protein 
                 BCAN 
               
               
                 Q96HF1 
                 Secreted frizzled-related protein 2 
                 SFRP2 
               
               
                 Q96I82 
                 Kazal-type serine protease inhibitor domain- 
                 KAZALD1 
               
               
                   
                 containing protein 1 
               
               
                 Q96ID5 
                 Immunoglobulin superfamily member 21 
                 IGSF21 
               
               
                 Q96II8 
                 Leucine-rich repeat and calponin homology 
                 LRCH3 
               
               
                   
                 domain-containing protein 3 
               
               
                 Q96IY4 
                 Carboxypeptidase B2 
                 CPB2 
               
               
                 Q96JB6 
                 Lysyl oxidase homolog 4 
                 LOXL4 
               
               
                 Q96JK4 
                 HHIP-like protein 1 
                 HHIPL1 
               
               
                 Q96KN2 
                 Beta-Ala-His dipeptidase 
                 CNDP1 
               
               
                 Q96KW9 
                 Protein SPACA7 
                 SPACA7 
               
               
                 Q96KX0 
                 Lysozyme-like protein 4 
                 LYZL4 
               
               
                 Q96L15 
                 Ecto-ADP-ribosyltransferase 5 
                 ART5 
               
               
                 Q96LB8 
                 Peptidoglycan recognition protein 4 
                 PGLYRP4 
               
               
                 Q96LB9 
                 Peptidoglycan recognition protein 3 
                 PGLYRP3 
               
               
                 Q96LC7 
                 Sialic acid-binding Ig-like lectin 10 
                 SIGLEC10 
               
               
                 Q96LR4 
                 Protein FAM19A4 
                 FAM19A4 
               
               
                 Q96MK3 
                 Protein FAM20A 
                 FAM20A 
               
               
                 Q96MS3 
                 Glycosyltransferase 1 domain-containing protein 1 
                 GLT1D1 
               
               
                 Q96NY8 
                 Processed poliovirus receptor-related protein 4 
                 PVRL4 
               
               
                 Q96NZ8 
                 WAP, kazal, immunoglobulin, kunitz and NTR 
                 WFIKKN1 
               
               
                   
                 domain-containing protein 1 
               
               
                 Q96NZ9 
                 Proline-rich acidic protein 1 
                 PRAP1 
               
               
                 Q96P44 
                 Collagen alpha-1(XXI) chain 
                 COL21A1 
               
               
                 Q96PB7 
                 Noelin-3 
                 OLFM3 
               
               
                 Q96PC5 
                 Melanoma inhibitory activity protein 2 
                 MIA2 
               
               
                 Q96PD5 
                 N-acetylmuramoyl-L-alanine amidase 
                 PGLYRP2 
               
               
                 Q96PH6 
                 Beta-defensin 118 
                 DEFB118 
               
               
                 Q96PL1 
                 Secretoglobin family 3A member 2 
                 SCGB3A2 
               
               
                 Q96PL2 
                 Beta-tectorin 
                 TECTB 
               
               
                 Q96QH8 
                 Sperm acrosome-associated protein 5 
                 SPACA5 
               
               
                 Q96QR1 
                 Secretoglobin family 3A member 1 
                 SCGB3A1 
               
               
                 Q96QU1 
                 Protocadherin-15 
                 PCDH15 
               
               
                 Q96QV1 
                 Hedgehog-interacting protein 
                 HHIP 
               
               
                 Q96RW7 
                 Hemicentin-1 
                 HMCN1 
               
               
                 Q96S42 
                 Nodal homolog 
                 NODAL 
               
               
                 Q96S86 
                 Hyaluronan and proteoglycan link protein 3 
                 HAPLN3 
               
               
                 Q96SL4 
                 Glutathione peroxidase 7 
                 GPX7 
               
               
                 Q96SM3 
                 Probable carboxypeptidase X1 
                 CPXM1 
               
               
                 Q96T91 
                 Glycoprotein hormone alpha-2 
                 GPHA2 
               
               
                 Q99062 
                 Granulocyte colony-stimulating factor receptor 
                 CSF3R 
               
               
                 Q99102 
                 Mucin-4 alpha chain 
                 MUC4 
               
               
                 Q99217 
                 Amelogenin, X isoform 
                 AMELX 
               
               
                 Q99218 
                 Amelogenin, Y isoform 
                 AMELY 
               
               
                 Q99435 
                 Protein kinase C-binding protein NELL2 
                 NELL2 
               
               
                 Q99470 
                 Stromal cell-derived factor 2 
                 SDF2 
               
               
                 Q99542 
                 Matrix metalloproteinase-19 
                 MMP19 
               
               
                 Q99574 
                 Neuroserpin 
                 SERPINI1 
               
               
                 Q99584 
                 Protein S100-A13 
                 S100A13 
               
               
                 Q99616 
                 C-C motif chemokine 13 
                 CCL13 
               
               
                 Q99645 
                 Epiphycan 
                 EPYC 
               
               
                 Q99674 
                 Cell growth regulator with EF hand domain 
                 CGREF1 
               
               
                   
                 protein 1 
               
               
                 Q99715 
                 Collagen alpha-1(XII) chain 
                 COL12A1 
               
               
                 Q99727 
                 Metalloproteinase inhibitor 4 
                 TIMP4 
               
               
                 Q99731 
                 C-C motif chemokine 19 
                 CCL19 
               
               
                 Q99748 
                 Neurturin 
                 NRTN 
               
               
                 Q99935 
                 Proline-rich protein 1 
                 PROL1 
               
               
                 Q99942 
                 E3 ubiquitin-protein ligase RNF5 
                 RNF5 
               
               
                 Q99944 
                 Epidermal growth factor-like protein 8 
                 EGFL8 
               
               
                 Q99954 
                 Submaxillary gland androgen-regulated protein 3A 
                 SMR3A 
               
               
                 Q99969 
                 Retinoic acid receptor responder protein 2 
                 RARRES2 
               
               
                 Q99972 
                 Myocilin 
                 MYOC 
               
               
                 Q99983 
                 Osteomodulin 
                 OMD 
               
               
                 Q99985 
                 Semaphorin-3C 
                 SEMA3C 
               
               
                 Q99988 
                 Growth/differentiation factor 15 
                 GDF15 
               
               
                 Q9BPW4 
                 Apolipoprotein L4 
                 APOL4 
               
               
                 Q9BQ08 
                 Resistin-like beta 
                 RETNLB 
               
               
                 Q9BQ16 
                 Testican-3 
                 SPOCK3 
               
               
                 Q9BQ51 
                 Programmed cell death 1 ligand 2 
                 PDCD1LG2 
               
               
                 Q9BQB4 
                 Sclerostin 
                 SOST 
               
               
                 Q9BQI4 
                 Coiled-coil domain-containing protein 3 
                 CCDC3 
               
               
                 Q9BQP9 
                 BPI fold-containing family A member 3 
                 BPIFA3 
               
               
                 Q9BQR3 
                 Serine protease 27 
                 PRSS27 
               
               
                 Q9BQY6 
                 WAP four-disulfide core domain protein 6 
                 WFDC6 
               
               
                 Q9BRR6 
                 ADP-dependent glucokinase 
                 ADPGK 
               
               
                 Q9BS86 
                 Zona pellucida-binding protein 1 
                 ZPBP 
               
               
                 Q9BSG0 
                 Protease-associated domain-containing protein 1 
                 PRADC1 
               
               
                 Q9BSG5 
                 Retbindin 
                 RTBDN 
               
               
                 Q9BT30 
                 Probable alpha-ketoglutarate-dependent 
                 ALKBH7 
               
               
                   
                 dioxygenase ABH7 
               
               
                 Q9BT56 
                 Spexin 
                 C12orG9 
               
               
                 Q9BT67 
                 NEDD4 family-interacting protein 1 
                 NDFIP1 
               
               
                 Q9BTY2 
                 Plasma alpha-L-fucosidase 
                 FUCA2 
               
               
                 Q9BU40 
                 Chordin-like protein 1 
                 CHRDL1 
               
               
                 Q9BUD6 
                 Spondin-2 
                 SPON2 
               
               
                 Q9BUN1 
                 Protein MENT 
                 MENT 
               
               
                 Q9BUR5 
                 Apolipoprotein O 
                 APOO 
               
               
                 Q9BV94 
                 ER degradation-enhancing alpha-mannosidase-like 2 
                 EDEM2 
               
               
                 Q9BWP8 
                 Collectin-11 
                 COLEC11 
               
               
                 Q9BWS9 
                 Chitinase domain-containing protein 1 
                 CHID1 
               
               
                 Q9BX67 
                 Junctional adhesion molecule C 
                 JAM3 
               
               
                 Q9BX93 
                 Group XIIB secretory phospholipase A2-like 
                 PLA2G12B 
               
               
                   
                 protein 
               
               
                 Q9BXI9 
                 Complement C1q tumor necrosis factor-related 
                 C1QTNF6 
               
               
                   
                 protein 6 
               
               
                 Q9BXJ0 
                 Complement C1q tumor necrosis factor-related 
                 C1QTNF5 
               
               
                   
                 protein 5 
               
               
                 Q9BXJ1 
                 Complement C1q tumor necrosis factor-related 
                 C1QTNF1 
               
               
                   
                 protein 1 
               
               
                 Q9BXJ2 
                 Complement C1q tumor necrosis factor-related 
                 C1QTNF7 
               
               
                   
                 protein 7 
               
               
                 Q9BXJ3 
                 Complement C1q tumor necrosis factor-related 
                 C1QTNF4 
               
               
                   
                 protein 4 
               
               
                 Q9BXJ4 
                 Complement C1q tumor necrosis factor-related 
                 C1QTNF3 
               
               
                   
                 protein 3 
               
               
                 Q9BXJ5 
                 Complement C1q tumor necrosis factor-related 
                 C1QTNF2 
               
               
                   
                 protein 2 
               
               
                 Q9BXN1 
                 Asporin 
                 ASPN 
               
               
                 Q9BXP8 
                 Pappalysin-2 
                 PAPPA2 
               
               
                 Q9BXR6 
                 Complement factor H-related protein 5 
                 CFHR5 
               
               
                 Q9BXS0 
                 Collagen alpha-1(XXV) chain 
                 COL25A1 
               
               
                 Q9BXX0 
                 EMILIN-2 
                 EMILIN2 
               
               
                 Q9BXY4 
                 R-spondin-3 
                 RSPO3 
               
               
                 Q9BY15 
                 EGF-like module-containing mucin-like hormone 
                 EMR3 
               
               
                   
                 receptor-like 3 subunit beta 
               
               
                 Q9BY50 
                 Signal peptidase complex catalytic subunit 
                 SEC11C 
               
               
                   
                 SEC11C 
               
               
                 Q9BY76 
                 Angiopoietin-related protein 4 
                 ANGPTL4 
               
               
                 Q9BYF1 
                 Processed angiotensin-converting enzyme 2 
                 ACE2 
               
               
                 Q9BYJ0 
                 Fibroblast growth factor-binding protein 2 
                 FGFBP2 
               
               
                 Q9BYW3 
                 Beta-defensin 126 
                 DEFB126 
               
               
                 Q9BYX4 
                 Interferon-induced helicase C domain-containing 
                 IFIH1 
               
               
                   
                 protein 1 
               
               
                 Q9BYZ8 
                 Regenerating islet-derived protein 4 
                 REG4 
               
               
                 Q9BZ76 
                 Contactin-associated protein-like 3 
                 CNTNAP3 
               
               
                 Q9BZG9 
                 Ly-6/neurotoxin-like protein 1 
                 LYNX1 
               
               
                 Q9BZJ3 
                 Tryptase delta 
                 TPSD1 
               
               
                 Q9BZM1 
                 Group XIIA secretory phospholipase A2 
                 PLA2G12A 
               
               
                 Q9BZM2 
                 Group IIF secretory phospholipase A2 
                 PLA2G2F 
               
               
                 Q9BZM5 
                 NKG2D ligand 2 
                 ULBP2 
               
               
                 Q9BZP6 
                 Acidic mammalian chitinase 
                 CHIA 
               
               
                 Q9BZZ2 
                 Sialoadhesin 
                 SIGLEC1 
               
               
                 Q9C0B6 
                 Protein FAM5B 
                 FAM5B 
               
               
                 Q9GZM7 
                 Tubulointerstitial nephritis antigen-like 
                 TINAGL1 
               
               
                 Q9GZN4 
                 Brain-specific serine protease 4 
                 PRSS22 
               
               
                 Q9GZP0 
                 Platelet-derived growth factor D, receptor-binding 
                 PDGFD 
               
               
                   
                 form 
               
               
                 Q9GZT5 
                 Protein Wnt-10a 
                 WNT10A 
               
               
                 Q9GZU5 
                 Nyctalopin 
                 NYX 
               
               
                 Q9GZV7 
                 Hyaluronan and proteoglycan link protein 2 
                 HAPLN2 
               
               
                 Q9GZV9 
                 Fibroblast growth factor 23 
                 FGF23 
               
               
                 Q9GZX9 
                 Twisted gastrulation protein homolog 1 
                 TWSG1 
               
               
                 Q9GZZ7 
                 GDNF family receptor alpha-4 
                 GFRA4 
               
               
                 Q9GZZ8 
                 Extracellular glycoprotein lacritin 
                 LACRT 
               
               
                 Q9H0B8 
                 Cysteine-rich secretory protein LCCL domain- 
                 CRISPLD2 
               
               
                   
                 containing 2 
               
               
                 Q9H106 
                 Signal-regulatory protein delta 
                 SIRPD 
               
               
                 Q9H114 
                 Cystatin-like 1 
                 CSTL1 
               
               
                 Q9H173 
                 Nucleotide exchange factor SIL1 
                 SIL1 
               
               
                 Q9H1E1 
                 Ribonuclease 7 
                 RNASE7 
               
               
                 Q9H1F0 
                 WAP four-disulfide core domain protein 10A 
                 WFDC10A 
               
               
                 Q9H1J5 
                 Protein Wnt-8a 
                 WNT8A 
               
               
                 Q9H1J7 
                 Protein Wnt-5b 
                 WNT5B 
               
               
                 Q9H1M3 
                 Beta-defensin 129 
                 DEFB129 
               
               
                 Q9H1M4 
                 Beta-defensin 127 
                 DEFB127 
               
               
                 Q9H1Z8 
                 Augurin 
                 C2orf40 
               
               
                 Q9H239 
                 Matrix metalloproteinase-28 
                 MMP28 
               
               
                 Q9H2A7 
                 C-X-C motif chemokine 16 
                 CXCL16 
               
               
                 Q9H2A9 
                 Carbohydrate sulfotransferase 8 
                 CHST8 
               
               
                 Q9H2R5 
                 Kallikrein-15 
                 KLK15 
               
               
                 Q9H2X0 
                 Chordin 
                 CHRD 
               
               
                 Q9H2X3 
                 C-type lectin domain family 4 member M 
                 CLEC4M 
               
               
                 Q9H306 
                 Matrix metalloproteinase-27 
                 MMP27 
               
               
                 Q9H324 
                 A disintegrin and metalloproteinase with 
                 ADAMTS10 
               
               
                   
                 thrombospondin motifs 10 
               
               
                 Q9H336 
                 Cysteine-rich secretory protein LCCL domain- 
                 CRISPLD1 
               
               
                   
                 containing 1 
               
               
                 Q9H3E2 
                 Sorting nexin-25 
                 SNX25 
               
               
                 Q9H3R2 
                 Mucin-13 
                 MUC13 
               
               
                 Q9H3U7 
                 SPARC-related modular calcium-binding protein 2 
                 SMOC2 
               
               
                 Q9H3Y0 
                 Peptidase inhibitor R3HDML 
                 R3HDML 
               
               
                 Q9H4A4 
                 Aminopeptidase B 
                 RNPEP 
               
               
                 Q9H4F8 
                 SPARC-related modular calcium-binding protein 1 
                 SMOC1 
               
               
                 Q9H4G1 
                 Cystatin-9-like 
                 CST9L 
               
               
                 Q9H5V8 
                 CUB domain-containing protein 1 
                 CDCP1 
               
               
                 Q9H6B9 
                 Epoxide hydrolase 3 
                 EPHX3 
               
               
                 Q9H6E4 
                 Coiled-coil domain-containing protein 134 
                 CCDC134 
               
               
                 Q9H741 
                 UPF0454 protein C12orf49 
                 C12orf49 
               
               
                 Q9H772 
                 Gremlin-2 
                 GREM2 
               
               
                 Q9H7Y0 
                 Deleted in autism-related protein 1 
                 CXorf36 
               
               
                 Q9H8L6 
                 Multimerin-2 
                 MMRN2 
               
               
                 Q9H9S5 
                 Fukutin-related protein 
                 FKRP 
               
               
                 Q9HAT2 
                 Sialate O-acetylesterase 
                 SIAE 
               
               
                 Q9HB40 
                 Retinoid-inducible serine carboxypeptidase 
                 SCPEP1 
               
               
                 Q9HB63 
                 Netrin-4 
                 NTN4 
               
               
                 Q9HBJ0 
                 Placenta-specific protein 1 
                 PLAC1 
               
               
                 Q9HC23 
                 Prokineticin-2 
                 PROK2 
               
               
                 Q9HC57 
                 WAP four-disulfide core domain protein 1 
                 WFDC1 
               
               
                 Q9HC73 
                 Cytokine receptor-like factor 2 
                 CRLF2 
               
               
                 Q9HC84 
                 Mucin-5B 
                 MUC5B 
               
               
                 Q9HCB6 
                 Spondin-1 
                 SPON1 
               
               
                 Q9HCQ7 
                 Neuropeptide NPSF 
                 NPVF 
               
               
                 Q9HCT0 
                 Fibroblast growth factor 22 
                 FGF22 
               
               
                 Q9HD89 
                 Resistin 
                 RETN 
               
               
                 Q9NNX1 
                 Tuftelin 
                 TUFT1 
               
               
                 Q9NNX6 
                 CD209 antigen 
                 CD209 
               
               
                 Q9NP55 
                 BPI fold-containing family A member 1 
                 BPIFA1 
               
               
                 Q9NP70 
                 Ameloblastin 
                 AMBN 
               
               
                 Q9NP95 
                 Fibroblast growth factor 20 
                 FGF20 
               
               
                 Q9NP99 
                 Triggering receptor expressed on myeloid cells 1 
                 TREM1 
               
               
                 Q9NPA2 
                 Matrix metalloproteinase-25 
                 MMP25 
               
               
                 Q9NPE2 
                 Neugrin 
                 NGRN 
               
               
                 Q9NPH0 
                 Lysophosphatidic acid phosphatase type 6 
                 ACP6 
               
               
                 Q9NPH6 
                 Odorant-binding protein 2b 
                 OBP2B 
               
               
                 Q9NQ30 
                 Endothelial cell-specific molecule 1 
                 ESM1 
               
               
                 Q9NQ36 
                 Signal peptide, CUB and EGF-like domain- 
                 SCUBE2 
               
               
                   
                 containing protein 2 
               
               
                 Q9NQ38 
                 Serine protease inhibitor Kazal-type 5 
                 SPINK5 
               
               
                 Q9NQ76 
                 Matrix extracellular phosphoglycoprotein 
                 MEPE 
               
               
                 Q9NQ79 
                 Cartilage acidic protein 1 
                 CRTAC1 
               
               
                 Q9NR16 
                 Scavenger receptor cysteine-rich type 1 protein 
                 CD163L1 
               
               
                   
                 M160 
               
               
                 Q9NR23 
                 Growth/differentiation factor 3 
                 GDF3 
               
               
                 Q9NR71 
                 Neutral ceramidase 
                 ASAH2 
               
               
                 Q9NR99 
                 Matrix-remodeling-associated protein 5 
                 MXRA5 
               
               
                 Q9NRA1 
                 Platelet-derived growth factor C 
                 PDGFC 
               
               
                 Q9NRC9 
                 Otoraplin 
                 OTOR 
               
               
                 Q9NRE1 
                 Matrix metalloproteinase-26 
                 MMP26 
               
               
                 Q9NRJ3 
                 C-C motif chemokine 28 
                 CCL28 
               
               
                 Q9NRM1 
                 Enamelin 
                 ENAM 
               
               
                 Q9NRN5 
                 Olfactomedin-like protein 3 
                 OLFML3 
               
               
                 Q9NRR1 
                 Cytokine-like protein 1 
                 CYTL1 
               
               
                 Q9NS15 
                 Latent-transforming growth factor beta-binding 
                 LTBP3 
               
               
                   
                 protein 3 
               
               
                 Q9NS62 
                 Thrombospondin type-1 domain-containing 
                 THSD1 
               
               
                   
                 protein 1 
               
               
                 Q9NS71 
                 Gastrokine-1 
                 GKN1 
               
               
                 Q9NS98 
                 Semaphorin-3G 
                 SEMA3G 
               
               
                 Q9NSA1 
                 Fibroblast growth factor 21 
                 FGF21 
               
               
                 Q9NT22 
                 EMILIN-3 
                 EMILIN3 
               
               
                 Q9NTU7 
                 Cerebellin-4 
                 CBLN4 
               
               
                 Q9NVR0 
                 Kelch-like protein 11 
                 KLHL11 
               
               
                 Q9NWH7 
                 Spermatogenesis-associated protein 6 
                 SPATA6 
               
               
                 Q9NXC2 
                 Glucose-fructose oxidoreductase domain- 
                 GFOD1 
               
               
                   
                 containing protein 1 
               
               
                 Q9NY56 
                 Odorant-binding protein 2a 
                 OBP2A 
               
               
                 Q9NY84 
                 Vascular non-inflammatory molecule 3 
                 VNN3 
               
               
                 Q9NZ20 
                 Group 3 secretory phospholipase A2 
                 PLA2G3 
               
               
                 Q9NZC2 
                 Triggering receptor expressed on myeloid cells 2 
                 TREM2 
               
               
                 Q9NZK5 
                 Adenosine deaminase CECR1 
                 CECR1 
               
               
                 Q9NZK7 
                 Group IIE secretory phospholipase A2 
                 PLA2G2E 
               
               
                 Q9NZP8 
                 Complement C1r subcomponent-like protein 
                 C1RL 
               
               
                 Q9NZV1 
                 Cysteine-rich motor neuron 1 protein 
                 CRIM1 
               
               
                 Q9NZW4 
                 Dentin sialoprotein 
                 DSPP 
               
               
                 Q9P0G3 
                 Kallikrein-14 
                 KLK14 
               
               
                 Q9P0W0 
                 Interferon kappa 
                 IFNK 
               
               
                 Q9P218 
                 Collagen alpha-1(XX) chain 
                 COL20A1 
               
               
                 Q9P2C4 
                 Transmembrane protein 181 
                 TMEM181 
               
               
                 Q9P2K2 
                 Thioredoxin domain-containing protein 16 
                 TXNDC16 
               
               
                 Q9P2N4 
                 A disintegrin and metalloproteinase with 
                 ADAMTS9 
               
               
                   
                 thrombospondin motifs 9 
               
               
                 Q9UBC7 
                 Galanin-like peptide 
                 GALP 
               
               
                 Q9UBD3 
                 Cytokine SCM-1 beta 
                 XCL2 
               
               
                 Q9UBD9 
                 Cardiotrophin-like cytokine factor 1 
                 CLCF1 
               
               
                 Q9UBM4 
                 Opticin 
                 OPTC 
               
               
                 Q9UBP4 
                 Dickkopf-related protein 3 
                 DKK3 
               
               
                 Q9UBQ6 
                 Exostosin-like 2 
                 EXTL2 
               
               
                 Q9UBR5 
                 Chemokine-like factor 
                 CKLF 
               
               
                 Q9UBS5 
                 Gamma-aminobutyric acid type B receptor subunit 
                 GABBR1 
               
               
                   
                 1 
               
               
                 Q9UBT3 
                 Dickkopf-related protein 4 short form 
                 DKK4 
               
               
                 Q9UBU2 
                 Dickkopf-related protein 2 
                 DKK2 
               
               
                 Q9UBU3 
                 Ghrelin-28 
                 GHRL 
               
               
                 Q9UBV4 
                 Protein Wnt-16 
                 WNT16 
               
               
                 Q9UBX5 
                 Fibulin-5 
                 FBLN5 
               
               
                 Q9UBX7 
                 Kallikrein-11 
                 KLK11 
               
               
                 Q9UEF7 
                 Klotho 
                 KL 
               
               
                 Q9UFP1 
                 Protein FAM198A 
                 FAM198A 
               
               
                 Q9UGM3 
                 Deleted in malignant brain tumors 1 protein 
                 DMBT1 
               
               
                 Q9UGM5 
                 Fetuin-B 
                 FETUB 
               
               
                 Q9UGP8 
                 Translocation protein SEC63 homolog 
                 SEC63 
               
               
                 Q9UHF0 
                 Neurokinin-B 
                 TAC3 
               
               
                 Q9UHF1 
                 Epidermal growth factor-like protein 7 
                 EGFL7 
               
               
                 Q9UHG2 
                 ProSAAS 
                 PCSK1N 
               
               
                 Q9UHI8 
                 A disintegrin and metalloproteinase with 
                 ADAMTS1 
               
               
                   
                 thrombospondin motifs 1 
               
               
                 Q9UHL4 
                 Dipeptidyl peptidase 2 
                 DPP7 
               
               
                 Q9UI42 
                 Carboxypeptidase A4 
                 CPA4 
               
               
                 Q9UIG4 
                 Psoriasis susceptibility 1 candidate gene 2 protein 
                 PSORS1C2 
               
               
                 Q9UIK5 
                 Tomoregulin-2 
                 TMEFF2 
               
               
                 Q9UIQ6 
                 Leucyl-cystinyl aminopeptidase, pregnancy serum 
                 LNPEP 
               
               
                   
                 form 
               
               
                 Q9UJA9 
                 Ectonucleotide 
                 ENPP5 
               
               
                   
                 pyrophosphatase/phosphodiesterase family 
               
               
                   
                 member 5 
               
               
                 Q9UJH8 
                 Meteorin 
                 METRN 
               
               
                 Q9UJJ9 
                 N-acetylglucosamine-1-phosphotransferase 
                 GNPTG 
               
               
                   
                 subunit gamma 
               
               
                 Q9UJW2 
                 Tubulointerstitial nephritis antigen 
                 TINAG 
               
               
                 Q9UK05 
                 Growth/differentiation factor 2 
                 GDF2 
               
               
                 Q9UK55 
                 Protein Z-dependent protease inhibitor 
                 SERPINA10 
               
               
                 Q9UK85 
                 Dickkopf-like protein 1 
                 DKKL1 
               
               
                 Q9UKJ1 
                 Paired immunoglobulin-like type 2 receptor alpha 
                 PILRA 
               
               
                 Q9UKP4 
                 A disintegrin and metalloproteinase with 
                 ADAMTS7 
               
               
                   
                 thrombospondin motifs 7 
               
               
                 Q9UKP5 
                 A disintegrin and metalloproteinase with 
                 ADAMTS6 
               
               
                   
                 thrombospondin motifs 6 
               
               
                 Q9UKQ2 
                 Disintegrin and metalloproteinase domain- 
                 ADAM28 
               
               
                   
                 containing protein 28 
               
               
                 Q9UKQ9 
                 Kallikrein-9 
                 KLK9 
               
               
                 Q9UKR0 
                 Kallikrein-12 
                 KLK12 
               
               
                 Q9UKR3 
                 Kallikrein-13 
                 KLK13 
               
               
                 Q9UKU9 
                 Angiopoietin-related protein 2 
                 ANGPTL2 
               
               
                 Q9UKZ9 
                 Procollagen C-endopeptidase enhancer 2 
                 PCOLCE2 
               
               
                 Q9UL52 
                 Transmembrane protease serine 11E non-catalytic 
                 TMPRSS11E 
               
               
                   
                 chain 
               
               
                 Q9ULC0 
                 Endomucin 
                 EMCN 
               
               
                 Q9ULI3 
                 Protein HEG homolog 1 
                 HEG1 
               
               
                 Q9ULZ1 
                 Apelin-13 
                 APLN 
               
               
                 Q9ULZ9 
                 Matrix metalloproteinase-17 
                 MMP17 
               
               
                 Q9UM21 
                 Alpha-1,3-mannosyl-glycoprotein 4-beta-N- 
                 MGAT4A 
               
               
                   
                 acetylglucosaminyltransferase A soluble form 
               
               
                 Q9UM22 
                 Mammalian ependymin-related protein 1 
                 EPDR1 
               
               
                 Q9UM73 
                 ALK tyrosine kinase receptor 
                 ALK 
               
               
                 Q9UMD9 
                 97 kDa linear IgA disease antigen 
                 COL17A1 
               
               
                 Q9UMX5 
                 Neudesin 
                 NENF 
               
               
                 Q9UN73 
                 Protocadherin alpha-6 
                 PCDHA6 
               
               
                 Q9UNA0 
                 A disintegrin and metalloproteinase with 
                 ADAMTS5 
               
               
                   
                 thrombospondin motifs 5 
               
               
                 Q9UNI1 
                 Chymotrypsin-like elastase family member 1 
                 CELA1 
               
               
                 Q9UNK4 
                 Group IID secretory phospholipase A2 
                 PLA2G2D 
               
               
                 Q9UP79 
                 A disintegrin and metalloproteinase with 
                 ADAMTS8 
               
               
                   
                 thrombospondin motifs 8 
               
               
                 Q9UPZ6 
                 Thrombospondin type-1 domain-containing 
                 THSD7A 
               
               
                   
                 protein 7A 
               
               
                 Q9UQ72 
                 Pregnancy-specific beta-1-glycoprotein 11 
                 PSG11 
               
               
                 Q9UQ74 
                 Pregnancy-specific beta-1-glycoprotein 8 
                 PSG8 
               
               
                 Q9UQC9 
                 Calcium-activated chloride channel regulator 2 
                 CLCA2 
               
               
                 Q9UQE7 
                 Structural maintenance of chromosomes protein 3 
                 SMC3 
               
               
                 Q9UQP3 
                 Tenascin-N 
                 TNN 
               
               
                 Q9Y223 
                 UDP-N-acetylglucosamine 2-epimerase 
                 GNE 
               
               
                 Q9Y240 
                 C-type lectin domain family 11 member A 
                 CLEC11A 
               
               
                 Q9Y251 
                 Heparanase 8 kDa subunit 
                 HPSE 
               
               
                 Q9Y258 
                 C-C motif chemokine 26 
                 CCL26 
               
               
                 Q9Y264 
                 Angiopoietin-4 
                 ANGPT4 
               
               
                 Q9Y275 
                 Tumor necrosis factor ligand superfamily member 
                 TNFSF13B 
               
               
                   
                 13b, membrane form 
               
               
                 Q9Y287 
                 BRI2 intracellular domain 
                 ITM2B 
               
               
                 Q9Y2E5 
                 Epididymis-specific alpha-mannosidase 
                 MAN2B2 
               
               
                 Q9Y334 
                 von Willebrand factor A domain-containing 
                 VWA7 
               
               
                   
                 protein 7 
               
               
                 Q9Y337 
                 Kallikrein-5 
                 KLK5 
               
               
                 Q9Y3B3 
                 Transmembrane emp24 domain-containing protein 7 
                 TMED7 
               
               
                 Q9Y3E2 
                 BolA-like protein 1 
                 BOLA1 
               
               
                 Q9Y426 
                 C2 domain-containing protein 2 
                 C2CD2 
               
               
                 Q9Y4K0 
                 Lysyl oxidase homolog 2 
                 LOXL2 
               
               
                 Q9Y4X3 
                 C-C motif chemokine 27 
                 CCL27 
               
               
                 Q9Y5C1 
                 Angiopoietin-related protein 3 
                 ANGPTL3 
               
               
                 Q9Y5I2 
                 Protocadherin alpha-10 
                 PCDHA10 
               
               
                 Q9Y5I3 
                 Protocadherin alpha-1 
                 PCDHA1 
               
               
                 Q9Y5K2 
                 Kallikrein-4 
                 KLK4 
               
               
                 Q9Y5L2 
                 Hypoxia-inducible lipid droplet-associated protein 
                 HILPDA 
               
               
                 Q9Y5Q5 
                 Atrial natriuretic peptide-converting enzyme 
                 CORIN 
               
               
                 Q9Y5R2 
                 Matrix metalloproteinase-24 
                 MMP24 
               
               
                 Q9Y5U5 
                 Tumor necrosis factor receptor superfamily 
                 TNFRSF18 
               
               
                   
                 member 18 
               
               
                 Q9Y5W5 
                 Wnt inhibitory factor 1 
                 WIF1 
               
               
                 Q9Y5X9 
                 Endothelial lipase 
                 LIPG 
               
               
                 Q9Y625 
                 Secreted glypican-6 
                 GPC6 
               
               
                 Q9Y646 
                 Carboxypeptidase Q 
                 CPQ 
               
               
                 Q9Y6C2 
                 EMILIN-1 
                 EMILIN1 
               
               
                 Q9Y6F9 
                 Protein Wnt-6 
                 WNT6 
               
               
                 Q9Y6I9 
                 Testis-expressed sequence 264 protein 
                 TEX264 
               
               
                 Q9Y6L7 
                 Tolloid-like protein 2 
                 TLL2 
               
               
                 Q9Y6N3 
                 Calcium-activated chloride channel regulator 
                 CLCA3P 
               
               
                   
                 family member 3 
               
               
                 Q9Y6N6 
                 Laminin subunit gamma-3 
                 LAMC3 
               
               
                 Q9Y6R7 
                 IgGFc-binding protein 
                 FCGBP 
               
               
                 Q9Y6Y9 
                 Lymphocyte antigen 96 
                 LY96 
               
               
                 Q9Y6Z7 
                 Collectin-10 
                 COLEC10 
               
               
                   
               
            
           
         
       
     
     In some embodiments, the compositions and methods of the invention provide for the delivery of one or more mRNAs encoding one or more additional exemplary proteins listed in Table 2; thus, compositions of the invention may comprise an mRNA encoding a protein listed in Table 2 (or a homolog thereof) along with other components set out herein, and methods of the invention may comprise preparing and/or administering a composition comprising an mRNA encoding a protein chosen from the proteins listed in Table 2 (or a homolog thereof) along with other components set out herein. 
     
       
         
           
               
             
               
                 TABLE 2 
               
             
            
               
                   
               
               
                 Additional Exemplary Proteins 
               
            
           
           
               
               
               
            
               
                 Uniprot ID 
                 Protein Name 
                 Gene Name 
               
               
                   
               
               
                 A6NGW2 
                 Putative stereocilin-like protein 
                 STRCP1 
               
               
                 A6NIE9 
                 Putative serine protease 29 
                 PRSS29P 
               
               
                 A6NJ16 
                 Putative V-set and immunoglobulin 
                 IGHV4OR15-8 
               
               
                   
                 domain-containing-like protein 
               
               
                   
                 IGHV4OR15-8 
               
               
                 A6NJS3 
                 Putative V-set and immunoglobulin 
                 IGHV1OR21-1 
               
               
                   
                 domain-containing-like protein 
               
               
                   
                 IGHV1OR21-1 
               
               
                 A6NMY6 
                 Putative annexin A2-like protein 
                 ANXA2P2 
               
               
                 A8MT79 
                 Putative zinc-alpha-2-glycoprotein-like 1 
               
               
                 A8MWS1 
                 Putative killer cell immunoglobulin-like 
                 KIR3DP1 
               
               
                   
                 receptor like protein KIR3DP1 
               
               
                 A8MXU0 
                 Putative beta-defensin 108A 
                 DEFB108P1 
               
               
                 C9JUS6 
                 Putative adrenomedullin-5-like protein 
                 ADM5 
               
               
                 P0C7V7 
                 Putative signal peptidase complex 
                 SEC11B 
               
               
                   
                 catalytic subunit SEC11B 
               
               
                 P0C854 
                 Putative cat eye syndrome critical region 
                 CECR9 
               
               
                   
                 protein 9 
               
               
                 Q13046 
                 Putative pregnancy-specific beta-1- 
                 PSG7 
               
               
                   
                 glycoprotein 7 
               
               
                 Q16609 
                 Putative apolipoprotein(a)-like protein 2 
                 LPAL2 
               
               
                 Q2TV78 
                 Putative macrophage-stimulating protein 
                 MST1P9 
               
               
                   
                 MSTP9 
               
               
                 Q5JQD4 
                 Putative peptide YY-3 
                 PYY3 
               
               
                 Q5R387 
                 Putative inactive group IIC secretory 
                 PLA2G2C 
               
               
                   
                 phospholipase A2 
               
               
                 Q5VSP4 
                 Putative lipocalin 1-like protein 1 
                 LCN1P1 
               
               
                 Q5W188 
                 Putative cystatin-9-like protein CST9LP1 
                 CST9LP1 
               
               
                 Q6UXR4 
                 Putative serpin A13 
                 SERPINA13P 
               
               
                 Q86SH4 
                 Putative testis-specific prion protein 
                 PRNT 
               
               
                 Q86YQ2 
                 Putative latherin 
                 LATH 
               
               
                 Q8IVG9 
                 Putative humanin peptide 
                 MT-RNR2 
               
               
                 Q8NHM4 
                 Putative trypsin-6 
                 TRY6 
               
               
                 Q8NHW4 
                 C-C motif chemokine 4-like 
                 CCL4L2 
               
               
                 Q9H7L2 
                 Putative killer cell immunoglobulin-like 
                 KIR3DX1 
               
               
                   
                 receptor-like protein KIR3DX1 
               
               
                 Q9NRI6 
                 Putative peptide YY-2 
                 PYY2 
               
               
                 Q9UF72 
                 Putative TP73 antisense gene protein 1 
                 TP73-AS1 
               
               
                 Q9UKY3 
                 Putative inactive carboxylesterase 4 
                 CES1P1 
               
               
                   
               
            
           
         
       
     
     The Uniprot IDs set forth in Table 1 and Table 2 refer to the human versions the listed proteins and the sequences of each are available from the Uniprot database. Sequences of the listed proteins are also generally available for various animals, including various mammals and animals of veterinary or industrial interest. Accordingly, in some embodiments, compositions and methods of the invention provide for the delivery of one or more mRNAs encoding one or more proteins chosen from mammalian homologs or homologs from an animal of veterinary cr industrial interest of the secreted proteins listed in Table 1 and Table 2; thus, compositions of the invention may comprise an mRNA encoding a protein chosen from mammalian homologs or homologs from an animal of veterinary or industrial interest of a protein listed in Table 1 and Table 2 along with other components set out herein, and methods of the invention may comprise preparing and/or administering a composition comprising an mRNA encoding a protein chosen from mammalian homologs or homologs from an animal of veterinary or industrial interest of a protein listed in Table 1 and Table 2 along with other components set out herein, In some embodiments, mammalian homologs are chosen from mouse, rat, hamster, gerbil, horse, pig, cow, llama, alpaca, mink, dog, cat, ferret, sheep, goat, or camel homologs. In some embodiments, the animal of veterinary or industrial interest is chosen from the mammals listed above and/or chicken, duck, turkey, salmon, catfish, or tilapia. 
     In embodiments, the compositions and methods of the invention provide for the delivery of mRNA encoding a lysosomal protein chosen from Table 3. In some embodiments, the compositions and methods of the invention provide for the delivery of one or more mRNAs encoding one or more lysosomal and/or related proteins listed in Table 3; thus, compositions of the invention may comprise an mRNA encoding a protein listed in Table 3 (or a homolog thereof) along with other components set out herein, and methods of the invention may comprise preparing and/or administering a composition comprising an mRNA encoding a protein chosen from the proteins listed in Table 3 (or a homolog thereof) along with other components set out herein. 
     
       
         
           
               
             
               
                 TABLE 3 
               
               
                   
               
               
                 Lysosomal and Related Proteins 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
            
               
                 α-fucosidase 
               
               
                 α-galactosidase 
               
               
                 α-glucosidase 
               
               
                 α-Iduronidase 
               
               
                 α-mannosidase 
               
               
                 α-N-acetylgalactosaminidase (α-galactosidase B) 
               
               
                 β-galactosidase 
               
               
                 β-glucuronidase 
               
               
                 β-hexosaminidase 
               
               
                 β-mannosidase 
               
               
                 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) lyase 
               
               
                 3-methylcrotonyl-CoA carboxylase 
               
               
                 3-O-sulfogalactosyl cerebroside sulfatase (arylsulfatase A) 
               
               
                 acetyl-CoA transferase 
               
               
                 acid alpha-glucosidase 
               
               
                 acid ceramidase 
               
               
                 acid lipase 
               
               
                 acid phosphatase 
               
               
                 acid sphingomyelinase 
               
               
                 alpha-galactosidase A 
               
               
                 arylsulfatase A 
               
               
                 beta-galactosidase 
               
               
                 beta-glucocerebrosidase 
               
               
                 beta-hexosaminidase 
               
               
                 biotinidase 
               
               
                 cathepsin A 
               
               
                 cathepsin K 
               
               
                 CLN3 
               
               
                 CLN5 
               
               
                 CLN6 
               
               
                 CLN8 
               
               
                 CLN9 
               
               
                 cystine transporter (cystinosin) 
               
               
                 cytosolic protein beta3A subunit of the adaptor protein-3 complex, AP3 
               
               
                 formyl-Glycine generating enzyme (FGE) 
               
               
                 Galactocerebrosidase 
               
               
                 galactose-1-phosphate uridyltransferase (GALT) 
               
               
                 galactose 6-sulfate sulfatase 
               
               
                 (also known as N-acetylgalactosamine-6-sulfatase) 
               
               
                 Glucocerebrosidase 
               
               
                 glucuronate sulfatase 
               
               
                 glucuronidase 
               
               
                 glycoprotein cleaving enzymes 
               
               
                 glycosaminoglycan cleaving enzymes 
               
               
                 glycosylasparaginase (aspartylglucosaminidase) 
               
               
                 GM2-AP 
               
               
                 Heparan-alpha-glucosaminide N-acetyltransferase (HGSNAT, TMEM76) 
               
               
                 Heparan sulfatase 
               
               
                 hexosaminidase A lysosomal proteases methylmalonyl-CoA mutase 
               
               
                 Hyaluronidase 
               
               
                 Iduronate sulfatase 
               
               
                 LAMP-2 
               
               
                 lysosomal α-mannosidase 
               
               
                 Lysosomal p40 (C2orf18) 
               
               
                 Major facilitator superfamily domain containing 8 protein 
               
               
                 (MFSD8 or CLN7) 
               
               
                 N-acetylgalactosamine 4-sulfatase 
               
               
                 N-acetyl glucosamine 6-sulfatase 
               
               
                 N-acetyl glucosaminidase 
               
               
                 N-acetylglucosamine-1-phosphate transferase 
               
               
                 NPC1 
               
               
                 NPC2 
               
               
                 palmitoyl-protein thioesterase 
               
               
                 palmitoyl-protein thioesterase (CLN1) 
               
               
                 Saposin A (Sphingolipid activator protein A) 
               
               
                 Saposin B (Sphingolipid activator protein B) 
               
               
                 Saposin C (Sphingolipid activator protein C) 
               
               
                 Saposin D (Sphingolipid activator protein D) 
               
               
                 sialic acid transporter (sialin) 
               
               
                 Sialidase 
               
               
                 Sialin 
               
               
                 Sulfatase 
               
               
                 Transmembrane protein 74 (TMEM74) 
               
               
                 tripeptidyl-peptidase 
               
               
                 tripeptidyl-peptidase I (CLN2) 
               
               
                 UDP-N-acetylglucosamine- phosphotransferase 
               
               
                   
               
            
           
         
       
     
     Information regarding lysosomal proteins is available from Lubke et al., “Proteomics of the LYsosome,”  Biochim Biophys Acta.  (2009) 1793: 625-635. In some embodiments, the protein listed in Table 3 and encoded by mRNA in the compositions and methods of the invention is a human protein. Sequences of the listed proteins are also available for various animals, including various mammals and animals of veterinary or industrial interest as described above. 
     In some embodiments, the compositions and methods of the invention provide for the delivery of mRNA encoding a therapeutic protein (e.g., cytosolic, transmembrane or secreted) such as those listed in Table 4. In some embodiments, the compositions and methods of the invention provide for the delivery of an mRNA encoding a therapeutic protein useful in treating a disease or disorder (i.e., indication) listed in Table 4; thus, compositions of the invention may comprise an mRNA encoding a therapeutic protein listed or not listed in Table 4 (or a homolog thereof, as discussed below) along with other components set out herein for treating a disease or disorder (i.e., indication) listed in Table 4, and methods of the invention may comprise preparing and/or administering a composition comprising an mRNA encoding a such a protein (or a homolog thereof, as discussed below) along with other components set out herein for treatment of a disease or disorder listed in Table 4. 
     
       
         
           
               
             
               
                 TABLE 4 
               
             
            
               
                   
               
               
                 Exemplary Indications and Related Proteins 
               
            
           
           
               
               
            
               
                 Indication 
                 Therapeutic Protein 
               
               
                   
               
               
                 3-Methylcrotonyl-CoA carboxylase deficiency 
                 Methylcrotonoyl-CoA carboxylase 
               
               
                 3-Methylglutaconic aciduria 
                 Methylglutaconyl-CoA hydratase 
               
               
                 Actinic keratosis 
               
               
                 Acute intermittent porphyria 
                 Porphobilinogen deaminase 
               
               
                 Acute lymphocytic leukemia 
               
               
                 Acute myeloid leukemia 
               
               
                 Addison&#39;s disease 
               
               
                 Adenosine deaminase deficiency 
                 Adenosine deaminase 
               
               
                 Adrenoleukodystrophy 
                 ABCD1 
               
               
                 Adrenomyeloneuropathy 
               
               
                 AIDS/HIV 
               
               
                 Alcohol use disorders 
               
               
                 Alkaptonuria 
                 Homogentisate 1,2-dioxygenase 
               
               
                 Allergic asthma 
                 Anti-IgE mAb 
               
               
                 Allergies (dermatitis, rhinitis) 
               
               
                 Alopecia areata 
               
               
                 Alpers&#39; disease 
                 POLG 
               
               
                 Alpers-Huttenlocher syndrome 
               
               
                 Alpha 1-antitrypsin deficiency 
                 Alpha 1 protease inhibitor 
               
               
                 Alpha-mannosidosis 
                 Alpha-D-mannosidase 
               
               
                 Alport syndrome 
               
               
                 Alzheimer&#39;s disease 
               
               
                 Amyloid light-chain amyloidosis 
               
               
                 Amyotrophic lateral sclerosis (ALS) 
               
               
                 Anemia 
                 Erythropoietin 
               
               
                 Aortic valve stenosis 
               
               
                 Argininemia 
                 Arginase 
               
               
                 Argininosuccinic acidemia 
                 Argininosuccinate lyase 
               
               
                 Arrhythmogenic right ventricular dysplasia 
               
               
                 Autism 
               
               
                 Autosomal dominant and recessive progressive 
               
               
                 external ophthalmoplegia with mitochondrial DNA 
               
               
                 deletions 
               
               
                 Autosomal recessive polycystic kidney disease 
                 ARPKD 
               
               
                 Bacterial infections 
               
               
                 Basal cell carcinoma 
               
               
                 Batten disease 
                 Battenin + others 
               
               
                 B-cell chronic lymphocytic leukemia 
               
               
                 Becker muscular dystrophy 
                 Dystrophin 
               
               
                 Beta-thalassemia 
                 Beta globin 
               
               
                 Binge eating disorder 
               
               
                 Bipolar disorder 
               
               
                 Bladder cancer 
               
               
                 Blepharospasm, Cervical dystonia, Chronic migraine, 
                 Botulinum toxin 
               
               
                 more 
               
               
                 Bronchiolitis obliterans 
               
               
                 Brugada syndrome 
               
               
                 Buerger&#39;s disease 
               
               
                 CACNA1A 
               
               
                 CACNB4-related Episodic Ataxia Type 2 
               
               
                 Cancer and depression 
               
               
                 Cancer and sexual dysfunction 
               
               
                 Cancer in pregnancy 
               
               
                 Carbamylphosphate synthetase deficiency 
                 Carbamylphosphate synthetase 
               
               
                 Carcinoma of the gallbladder 
               
               
                 Cardiomyopathy (diabetic) 
               
               
                 Cardiomyopathy (hypertrophic) 
               
               
                 Carnitine uptake defect 
                 SLC22A5 
               
               
                 Catecholaminergic polymorphic ventricular 
               
               
                 tachycardia 
               
               
                 CDKL5-related Atypical Rett Syndrome 
               
               
                 Celiac disease 
               
               
                 Cellulitis 
               
               
                 Cerebrovascular disease 
               
               
                 Cervix uteri cancer 
               
               
                 Chronic fatigue syndrome 
               
               
                 Chronic graft versus host disease 
               
               
                 Chronic idiopathic urticaria 
               
               
                 Chronic immune thrombocytopenia 
                 Thrombopoietin 
               
               
                 Chronic kidney kisease 
               
               
                 Chronic liver disease 
               
               
                 Chronic lymphocytic leukemia 
               
               
                 Chronic myeloid leukemia 
               
               
                 Chronic pancreatitis 
               
               
                 Cirrhosis of the liver 
               
               
                 Citrullinemia, type I 
                 Argininosuccinate synthase 
               
               
                 Classic Rett Syndrome 
               
               
                 Classical galactosemia 
                 Galactose-1-phosphate uridylyltransferase 
               
               
                 Clostridium difficile associated diarrhea 
               
               
                 Clotting disorders 
               
               
                 COAD/COPD 
               
               
                 Cocaine addiction 
               
               
                 COL4A5-related disorders 
               
               
                 Cold contact urticaria 
               
               
                 Contraception, female 
               
               
                 Coronary artery diseases 
               
               
                 Corpus uteri cancer 
               
               
                 Corticobasal degeneration 
               
               
                 Crigler-Najjar syndrome 
                 UDP-glucuronosyltransferase 
               
               
                 Critical limb ischemia 
               
               
                 CTNS-related cystinosis 
               
               
                 Cutaneous lupus erythematosus 
               
               
                 Cutaneous neuroendocrine carcinoma (Merkel Cell) 
               
               
                 Cystic fibrosis 
                 CFTR 
               
               
                 Cystic fibrosis 
                 Deoxyribonuclease I 
               
               
                 Cystinosis 
                 Cystinosin 
               
               
                 Cystinuria 
                 SLC7A9 
               
               
                 Dementia (Lewy body) 
               
               
                 Depression 
               
               
                 Diabetic foot infections 
               
               
                 Diabetic foot ulcer 
               
               
                 Diabetic peripheral neuropathy 
               
               
                 Diabetic ulcers 
               
               
                 Diarrhoeal diseases 
               
               
                 Diffuse large B-cell lymphoma 
               
               
                 DiGeorge syndrome 
               
               
                 Diverticulitis 
               
               
                 Drug use disorders 
               
               
                 Duchenne muscular dystrophy 
                 Dystrophin 
               
               
                 Dysarthria 
               
               
                 Dyskinesia (levodopa-induced) 
               
               
                 Early-onset autosomal dominant Alzheimer&#39;s disease 
               
               
                 Eczema 
               
               
                 Ehlers-Danlos syndrome, type 1 
               
               
                 EIF2B1 
               
               
                 EIF2B2 
               
               
                 EIF2B3 
               
               
                 EIF2B4 
               
               
                 EIF2B5-related childhood ataxia with central nervous 
               
               
                 system hypomyelination/vanishing white matter 
               
               
                 Eosinophilic esophagitis 
               
               
                 Epilepsy 
               
               
                 Erectile dysfunction 
               
               
                 Erythropoietic protoporphyria 
                 Ferrochelatase 
               
               
                 Esophageal carcinoma 
               
               
                 Essential tremor 
               
               
                 Fabry disease 
                 Alpha galactosidase 
               
               
                 Familial adenomatous polyposis 
                 APC 
               
               
                 Familial chylomicronemia 
                 Lipoprotein lipase 
               
               
                 Familial dysbetalipoproteinemia 
                 Apolipoprotein E 
               
               
                 Familial isolated dilated cardiomyopathy 
               
               
                 Familial mediterranean fever 
                 Pyrin (MEFV) 
               
               
                 Familial melanoma 
               
               
                 Female infertility 
                 Follicle stimulating hormone 
               
               
                 Female sexual dysfunction 
               
               
                 Fibromyalgia 
               
               
                 FMR1-related disorders 
               
               
                 Fracture healing 
               
               
                 Fragile X Premature Ovarian Failure Syndrome 
               
               
                 Fragile X syndrome 
                 FMRP 
               
               
                 Fragile X-Associated Tremor/Ataxia Syndrome 
               
               
                 Friedreich&#39;s ataxia 
               
               
                 Frontotemporal dementia 
               
               
                 Fryns syndrome 
               
               
                 Galactocerebrosidase deficiencies 
               
               
                 GALE deficiency 
                 Galactose epimerase 
               
               
                 GALK deficiency 
                 Galactokinase 
               
               
                 GALT-related galactosemia 
               
               
                 Gastric cancer 
               
               
                 Gastroesophageal reflux disease 
               
               
                 Gaucher disease 
                 Glucocerebrosidase 
               
               
                 Gilbert syndrome 
                 UDP-glucuronosyltransferase 
               
               
                 Glioblastoma multiforme 
               
               
                 Glomerulonephritis 
               
               
                 Glutaric acidemia, type I 
                 Glutaryl-CoA dehydrogenase 
               
               
                 GM2 gangliosidosis 
                 HEXA, HEXB 
               
               
                 Gout 
                 Urate oxidase 
               
               
                 Graft versus host disease 
               
               
                 Growth hormone deficiency 
                 Growth hormone 1/Growth hormone 2 
               
               
                 Head and neck cancer, Metastatic colorectal cancer 
                 Anti-EGFr mAb 
               
               
                 Hearing loss, adult onset 
               
               
                 Heart failure 
               
               
                 Hemachromatosis 
                 HFE protein 
               
               
                 Hemifacial spasm 
               
               
                 Hemolytic uremic syndrome 
                 Anti-complement factor C5 mAb 
               
               
                 Hemophilia A 
                 Factor VIII 
               
               
                 Hemophilia A, Hemophilia B 
                 Factor VII 
               
               
                 Hemophilia B 
                 Factor IX 
               
               
                 Hepatitis B, Hepatitis C 
                 Interferon alpha 
               
               
                 HER2+ breast cancer, gastric cancer 
                 Anti-HER2 mAb 
               
               
                 Hereditary angioedema 
                 C1 esterase inhibitor 
               
               
                 Hereditary hemorrhagic telangiectasia 
               
               
                 Hereditary hemorrhagic telangiectasia (AT) 
               
               
                 Hereditary spherocytosis 
               
               
                 Hidradenitis suppurativa 
               
               
                 Homocystinuria 
                 Cystathionine beta-synthase 
               
               
                 Homozygous familial hypercholesterolemia 
                 LDL receptor 
               
               
                 Hunter syndrome (MPS II) 
                 Iduronate-2-sulfatase 
               
               
                 Huntington disease 
                 Huntingtin 
               
               
                 Hurler syndrome (MPS I) 
                 Alpha-L iduronidase 
               
               
                 Hydrolethalus 
               
               
                 Hyperalgesia 
               
               
                 Hyperbilirubinemia 
               
               
                 Hyperhidrosis 
               
               
                 Hyperlipidemia 
               
               
                 Hypermethioninemia 
                 Methionine adenosyltransferase 
               
               
                 Hyperoxaluria, type I 
                 Serine-pyruvate aminotransferase 
               
               
                 Hypertension 
               
               
                 Hyperuricemia 
               
               
                 Hyponatremia 
               
               
                 Hypoparathyroidism 
                 Parathyroid hormone 
               
               
                 Hypophosphatasia 
                 TNSALP 
               
               
                 Idiopathic pulmonary fibrosis 
               
               
                 Iminoglycinuria 
               
               
                 Immunoglobulin deficiency 
                 Immunoglobulin 
               
               
                 Infection (adenovirus) 
               
               
                 Infection (anthrax prophylaxis) 
               
               
                 Infection (BK virus) 
               
               
                 Infection (Clostridium difficile prophylaxis) 
               
               
                 Infection (Dengue fever prophylaxis) 
               
               
                 Infection (Epstein-Barr virus) 
               
               
                 Infection (Hepatitis-D) 
               
               
                 Infection (Lyme disease prophylaxis) 
               
               
                 Infection (Smallpox virus) 
               
               
                 Infectious diseases vaccines 
                 Infectious antigen 
               
               
                 Inflammatory heart diseases 
               
               
                 Insomnia 
               
               
                 Interstitial cystitis 
               
               
                 Iron-deficiency anaemia 
               
               
                 Irritable bowel disease 
               
               
                 Ischaemic heart disease 
               
               
                 Isovaleric aciduria 
                 Isovaleric acid CoA dehydrogenase deficiency 
               
               
                 Jansky-Bielschowsky disease 
               
               
                 Juvenile Batten disease 
               
               
                 Juvenile Neuronal Ceroid Lipofuscinosis (JNCL) 
               
               
                 Juvenile rheumatoid arthritis 
                 TNF-alpha inhibitors 
               
               
                 Kennedy&#39;s disease (SBMA) 
               
               
                 Keratoconus 
               
               
                 Krabbe disease 
                 Galactocerebrosidase 
               
               
                 Leber&#39;s hereditary optic neuropathy 
                 NADH dehydrogenase 
               
               
                 Leiomyosarcoma 
               
               
                 Lennox-Gastaut syndrome 
               
               
                 Lesch-Nyhan syndrome 
                 Hypoxanthine phosphoribosyltransferase 1 
               
               
                 Leukaemia 
               
               
                 Li-Fraumeni syndrome 
                 TP53 
               
               
                 Lipoma 
               
               
                 Liposarcoma 
               
               
                 Liver cancer 
               
               
                 Long-chain 3-OH acyl-CoA dehydrogenase deficiency 
                 Long-chain-3-hydroxyacyl-CoA dehydrogenase 
               
               
                 Lower respiratory infections 
               
               
                 Lysosomal acid lipase deficiency 
                 Lysosomal acid lipase 
               
               
                 Macular degeneration 
               
               
                 Major depressive disorder 
               
               
                 Malignant fibrous histiocytoma 
               
               
                 Mantle cell lymphoma 
               
               
                 Maple syrup urine disease 
                 3-methyl-2-oxobutanoate dehydrogenase 
               
               
                 Marfan syndrome 
                 FBN1 
               
               
                 Maroteaux-Lamy syndrome (MPS VI) 
                 N-acetylgalactosamine 4-sulfatase 
               
               
                 Mastocytosis 
               
               
                 McArdle disease 
                 Muscle glycogen phosphorylase 
               
               
                 MECP2-related disorders 
               
               
                 MECP2-related Severe Neonatal Encephalopathy 
               
               
                 Medium-chain acyl-CoA dehydrogenase deficiency 
                 Acyl-CoA dehydrogenase 
               
               
                 Melanoma 
                 Anti-CTLA4 mAb 
               
               
                 Metachromatic leukodystrophy 
                 Arylsulfatase A 
               
               
                 Metastatic colorectal cancer, NSCLC, others 
                 Anti-VEGF mAb 
               
               
                 Methylmalonyl-CoA mutase deficiency 
                 Methylmalonyl-CoA mutase 
               
               
                 Migraine 
               
               
                 Mitochondrial oxidative phosphorylation disorders 
               
               
                 Morquio syndrome, type A (MPS IVA) 
                 Galactose 6-sulfate sulfatase 
               
               
                 Morquio syndrome, type B (MPS IVB) 
                 Beta-galactosidase 
               
               
                 Mouth and oropharynx cancers 
               
               
                 Multiple carboxylase deficiency 
                 Biotin-methylcrotonoyl-CoA-carboxylase ligase 
               
               
                 Multiple myeloma 
               
               
                 Multiple sclerosis 
                 Anti-VLA-4 mAb 
               
               
                 Multiple sclerosis 
                 Interferon beta 
               
               
                 Multiple system atrophy 
               
               
                 Myasthenia gravis 
               
               
                 Myelofibrosis 
               
               
                 Narcolepsy 
               
               
                 Neonatal bronchopulmonary dysplasia 
               
               
                 Neonatal infections 
               
               
                 Nephritis and nephrosis 
               
               
                 Neurofibromatosis, type 1 
                 NF-1 
               
               
                 Neuronal ceroid lipofuscinoses-related diseases 
               
               
                 Neutropenia 
                 G-CSF 
               
               
                 Niemann Pick disease, type A/B 
                 SMPD1 
               
               
                 Niemann Pick disease, type C 
                 NPC1 
               
               
                 Niemann-Pick disease Type C1 
               
               
                 Nocturia 
               
               
                 Non-alcoholic fatty liver disease 
               
               
                 Non-Hodgkin lymphoma 
                 Anti-CD20 mAb 
               
               
                 Non-small cell lung cancer 
               
               
                 Notch-3 related cerebral autosomal dominant 
               
               
                 arteriopathy with subcortical infarcts and 
               
               
                 leukoencephalopathy (CADASIL) 
               
               
                 Obesity 
               
               
                 Ophthalmoparesis 
               
               
                 Opioid induced constipation 
               
               
                 Ornithine transcarbamylase deficiency 
                 Ornithine transcarbamylase 
               
               
                 Osteoarthritis 
               
               
                 Osteopetrosis 
               
               
                 Osteoporosis 
                 Anti-RANKL mAb 
               
               
                 Ovarian cancer 
               
               
                 Paget disease of bone 
                 Sequestosome 1 
               
               
                 Pain 
               
               
                 Pancreatic carcinoma 
               
               
                 Panic disorder 
               
               
                 Parkinson disease 
               
               
                 Paroxysmal nocturnal hemoglobinuria 
                 Anti-complement factor C5 Mab 
               
               
                   Pediculosis capitis  (head lice) 
               
               
                 Pelizaeus-Merzbacher disease 
               
               
                 Pemphigus vulgaris 
               
               
                 Peptic ulcer disease 
               
               
                 Peripheral neuropathy 
               
               
                 Peyronie&#39;s disease 
               
               
                 Phenylketonuria 
                 Phenylalanine hydroxylase 
               
               
                 Pneumococcal infection prophylaxis 
               
               
                 POLG-related sensory ataxic neuropathy 
               
               
                 Polycystic kidney disease 
               
               
                 Polycystic ovary syndrome 
               
               
                 Polycythaemia vera 
               
               
                 Polymerase G-related disorders 
               
               
                 Polymorphous light eruption 
               
               
                 Pompe disease 
                 Alpha glucosidase 
               
               
                 Porphyria cutanea tarda 
                 Uroporphyrinogen decarboxylase 
               
               
                 Post herpetic neuralgia 
               
               
                 Post-organ transplant 
               
               
                 Pouchitis 
               
               
                 PPM-X Syndrome 
               
               
                 Prader-Willi syndrome 
               
               
                 Preeclampsia 
               
               
                 Premature ejaculation 
               
               
                 Prematurity and low birth weight 
               
               
                 Primary ciliary dyskinesia 
                 DNAH5, DNAI1 
               
               
                 Primary glomerular diseases 
               
               
                 Primary humoral immune deficiencies (e.g., CVID) 
                 Immunoglobulin 
               
               
                 Proctitis 
               
               
                 Progressive familial intrahepatic cholestasis (PFIC) 
                 FIC1, BSEP, MDR3 
               
               
                 Progressive multifocal leukoencephalopathy 
               
               
                 Progressive supranuclear palsy 
               
               
                 Propionic acidemia 
                 Propionyl-CoA carboxylase 
               
               
                 Prostate cancer 
               
               
                 Psoriasis 
                 Anti-IL-12 &amp; IL-23 mAb 
               
               
                 Psoriatic arthritis 
                 TNF-alpha inhibitors 
               
               
                 PTT-1 
               
               
                 Pulmonary arterial hypertension 
               
               
                 Pulmonary arterial hypertension 
               
               
                 Raynaud&#39;s phenomenon 
               
               
                 Refractive errors 
               
               
                 Renal cell carcinoma 
               
               
                 Restless leg syndrome 
               
               
                 Retinitis pigmentosa 
               
               
                 Rheumatic heart disease 
               
               
                 Rheumatoid arthritis 
                 Anti-interleukin-6 (IL-6) mAb 
               
               
                 Rheumatoid arthritis 
                 T-cell costimulation blocker 
               
               
                 Rheumatoid arthritis 
                 TNF-alpha inhibitor 
               
               
                 Romano-Ward syndrome 
               
               
                 Rosacea 
               
               
                 Sanfilippo syndrome, type A (MPS IIIA) 
                 Heparan N-sulfatase 
               
               
                 Sanfilippo syndrome, type B (MPS IIIB) 
                 N-acetyl-alpha-D-glucosaminidase 
               
               
                 Santavuori-Haltia disease 
               
               
                 Schizophrenia 
               
               
                 Schnitzler syndrome 
               
               
                 Scleroderma 
               
               
                 SCN1A 
               
               
                 SCN1B-related seizure disorders 
               
               
                 Short-chain acyl-CoA dehydrogenase deficiency 
                 Butyryl-CoA dehydrogenase 
               
               
                 Sickle cell disease 
                 Hemoglobin 
               
               
                 SLC3A1-related disorders 
               
               
                 Small cell lung cancer 
               
               
                 SMN-1-related spinal muscular atrophy (SMA) 
               
               
                 Spinal muscular atrophy 
                 Survival motor neuron protein 
               
               
                 Squamous cell carcinoma of head and neck 
               
               
                 Stickler syndrome 
               
               
                 Stomach cancer 
               
               
                 Stroke prophylaxis 
               
               
                 Surfactant deficiency 
               
               
                 Synovial sarcoma 
               
               
                 Systemic lupus erythematosus 
                 Anti-BAFF 
               
               
                 Systemic sclerosis 
               
               
                 Tetrahydrobiopterin-deficient hyperphenylalaninemia 
                 Tetrahydrobiopterin 
               
               
                 Thromboangiitis obliterans 
               
               
                 Thrombotic disorders 
               
               
                 Thyroid cancer 
               
               
                 TPP1 deficiencies 
               
               
                 Trachea, bronchus, lung cancers 
               
               
                 Tricuspid atresia 
               
               
                 TSC1 
               
               
                 TSC2-related tuberous sclerosis 
               
               
                 Type 2 diabetes mellitus 
                 Glucagon-like peptide 1 (GLP-1) agonist 
               
               
                 Type 2 diabetes mellitus 
                 Insulin 
               
               
                 Tyrosinemia, type I 
                 Fumarylacetoacetase 
               
               
                 Ulcerative colitis 
               
               
                 Uterine fibroids 
               
               
                 Varicose veins 
               
               
                 Venous thromboembolism 
               
               
                 Very long-chain acyl-CoA dehydrogenase deficiency 
                 Long-chain-acyl-CoA dehydrogenase 
               
               
                 von Gierke&#39;s disease 
                 Glucose-6-phosphatase 
               
               
                 Von Hippel-Lindau disease 
                 pVHL 
               
               
                 Wegener granulomatosis 
               
               
                 Wilson disease 
                 Wilson disease protein 
               
               
                 X-Linked adrenal hypoplasia 
               
               
                 X-linked adrenoleukodystrophy 
               
               
                 X-linked agammaglobulinemia 
                 Bruton&#39;s tyrosine kinase 
               
               
                   
               
            
           
         
       
     
     In some embodiments, the present invention is used to prevent, treat, and/or cure a subject affected with a disease or disorder listed or associated with the proteins listed in Tables 1, 2, 3, or 4. In some embodiments, an mRNA encodes one or more of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR), argininosuccinate synthetase (ASS1), Factor IX, survival motor neuron 1 (SMN1), or phenylalanine hydroxylase (PAH). 
     Delivery Methods 
     The route of delivery used in the methods of the invention allows for non-invasive, self-administration of the compounds of the invention (e.g., a compound of Formula (A), such as any of Formulae (I)-(VII) or any one of Compounds 1-63). In some embodiments, the methods involve intratracheal or pulmonary administration by aerosolization, nebulization, or instillation of a compositions comprising mRNA encoding a therapeutic protein in a suitable transfection or lipid carrier vehicles as described above. In some embodiments, the protein is encapsulated with a liposome. In some embodiments, the liposome comprises a lipid, which is a compound of the invention (e.g., a compound of Formula (A), such as any of Formulae (I)-(VII) or any one of Compounds 1-63). As used herein below, administration of a compound of the invention includes administration of a composition comprising a compound of the invention. 
     Although the local cells and tissues of the lung represent a potential target capable of functioning as a biological depot or reservoir for production and secretion of the protein encoded by the mRNA, applicants have discovered that administration of the compounds of the invention (e.g., a compound of Formula (A), such as any of Formulae (I)-(VII) or any one of Compounds 1-63) to the lung via aerosolization, nebulization, or instillation results in the distribution of even non-secreted proteins outside the lung cells. Without wishing to be bound by any particular theory, it is contemplated that nanoparticle compositions of the invention pass, through the lung airway-blood barrier, resulting in translation of the intact nanoparticle to non-lung cells and tissues, such as, e.g., the heart, the liver, the spleen, where it results in the production of the encoded protein in these non-lung tissues. Thus, the utility of the compounds of the invention (e.g., a compound of Formula (A), such as any of Formulae (I)-(VII) or any one of Compounds 1-63) and methods of the invention extend beyond production of therapeutic protein in lung cells and tissues of the lung and can be used to delivery to non-lung target cells and/or tissues. They are useful in the management and treatment of a large number of diseases, and in particular peripheral diseases which result from both secreted and non-secreted protein and/or enzyme deficiencies (e.g., one or more lysosomal storage disorders). In certain embodiments, the compounds of the invention (e.g., a compound of Formula (A), such as any of Formulae (I)-(VII) or any one of Compounds 1-63), used in the methods of the invention result in the distribution of the mRNA encapsulated nanoparticles and production of the encoded protein in the liver, spleen, heart, and/or other non-lung cells. For example, administration of the compounds of the invention (e.g., a compound of Formula (A), such as any of Formulae (I)-(VII) or any one of Compounds 1-63), by aerosolization, nebulization, or instillation to the lung will result in the composition itself and its protein product (e.g., functional beta galactosidase protein) will be detectable in both the local cells and tissues of the lung, as well as in peripheral target cells, tissues and organs as a result of translocation of the mRNA and delivery vehicle to non-lung cells. 
     In certain embodiments, the compounds of the invention (e.g., a compound of Formula (A), such as any of Formulae (I)-(VII) or any one of Compounds 1-63) may be employed in the methods of the invention to specifically target peripheral cells or tissues. Following the pulmonary delivery, it is contemplated the compounds of the invention (e.g., a compound of Formula (A), such as any of Formulae (I)-(VII) or any one of Compounds 1-63) cross the lung airway-blood barrier and distribute into cells other than the local lung cells. Accordingly, the compounds disclosed herein (e.g., a compound of Formula (A), such as any of Formulae (I)-(VII) or any one of Compounds 1-63) may be administered to a subject by way of the pulmonary route of administration, using a variety of approach known by those skilled in the art (e.g., by inhalation), and distribute to both the local target cells and tissues of the lung, as well as in peripheral non-lung cells and tissues (e.g., cells of the liver, spleen, kidneys, heart, skeletal muscle, lymph nodes, brain, cerebrospinal fluid, and plasma). As a result, both the local cells of the lung and the peripheral non-lung cells can serve as biological reservoirs or depots capable of producing and/or secreting a translation product encoded by one or more polynucleotides. Accordingly, the present invention is not limited to the treatment of lung diseases or conditions, but rather can be used as a non-invasive means of facilitating the delivery of polynucleotides, or the production cf enzymes and proteins encoded thereby, in peripheral organs, tissues and cells (e.g., hepatocytes) which would otherwise be achieved only by systemic administration. Exemplary peripheral non-lung cells include, but are not limited to, hepatocytes, epithelial cells, hematopoietic cells, epithelial cells, endothelial cells, bone cells, stem cells, mesenchymal cells, neural cells, cardiac cells, adipocytes, vascular smooth muscle cells, cardiomyocytes, skeletal muscle cells, beta cells, pituitary cells, synovial lining cells, ovarian cells, testicular cells, fibroblasts, B cells, T cells, reticulocytes, leukocytes, granulocytes and tumor cells. 
     Following administration of the composition to the subject, the protein product encoded by the mRNA (e.g., a functional protein or enzyme) is detectable in the peripheral target tissues for at least about one to seven days or longer following administration of the compound to the subject. The amount of protein product necessary to achieve a therapeutic effect will vary depending on the condition being treated, the protein encoded, and the condition of the patient. For example, the protein product may be detectable in the peripheral target tissues at a concentration (e.g., a therapeutic concentration) of at least 0.025-1.5 μg/ml (e.g., at least 0.050 μg/ml, at least 0.075 μg/ml, at least 0.1 μg/ml, at least 0.2 μg/ml, at least 0.3 μg/ml, at least 0.4 μg/ml, at least 0.5 μg/ml, at least 0.6 μg/ml, at least 0.7 μg/ml, at least 0.8 μg/ml, at least 0.9 μg/ml, at least 1.0 μg/ml, at least 1.1 μg/ml, at least 1.2 μg/ml at least 1.3 μg/ml, at least 1.4 μg/ml, or at least 1.5 μg/ml), for at least about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11,12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 35, 40, 45 days or longer following administration of the compound to the subject. 
     It has been demonstrated that nucleic acids can be delivered to the lungs by intratracheal administration of a liquid suspension of the compound and inhalation of an aerosol mist produced by a liquid nebulizer or the use of a dry powder apparatus such as that described in U.S. Pat. No. 5,780,014, incorporated herein by reference, 
     In certain embodiments, the compounds of the invention (e.g., a compound of Formula (A), such as any of Formulae (I)-(VII) or any one of Compounds 1-63) may be formulated such that they may be aerosolized or otherwise delivered as a particulate liquid or solid prior to or upon administration to the subject. Such compounds may be administered with the assistance of one or more suitable devices for administering such solid or liquid particulate compositions (such as, e.g., an aerosolized aqueous solution or suspension) to generate particles that are easily respirable or inhalable by the subject. In some embodiments, such devices (e.g., a metered dose inhaler, jet-nebulizer, ultrasonic nebulizer, dry-powder-inhalers, propellant-based inhaler or an insufflator) facilitate the administration of a predetermined mass, volume or dose of the compositions (e.g., about 0.5 mg/kg of mRNA per dose) to the subject. For example, in certain embodiments, the compounds of the invention (e.g., a compound of Formula (A), such as any of Formulae (I)-(VII) or any one of Compounds 1-63) are administered to a subject using a metered dose inhaler containing a suspension or solution comprising the compound and a suitable propellant. In certain embodiments, the compounds of the invention (e.g., a compound of Formula (A), such as any of Formulae (I)-(VII) or any one of Compounds 1-63) may be formulated as a particulate powder (e.g., respirable dry particles) intended for inhalation, n certain embodiments, compositions of the invention formulated as respirable particles are appropriately sized such that they may be respirable by the subject or delivered using a suitable device (e.g., a mean D50 or D90 particle size less than about 500 μm, 400 μm, 300 μm, 250 μm, 200μm, 150 μm, 100 μm, 75 μm, 50 μm, 25 μm, 20 μm, 15 μm, 12.5 μm, 10 μm, 5 μm, 2.5 μm or smaller). In yet other embodiments, the compounds of the invention (e.g., a compound of Formula (A), such as any of Formulae (I)-(VII) or any one of Compounds 1-63) are formulated to include one or more pulmonary surfactants (e.g., lamellar bodies). In some embodiments, the compounds of the invention (e.g., a compound of Formula (A), such as any of Formulae (I)-(VII) or any one of Compounds 1-63) are administered to a subject such that a concentration of at least 0.05 mg/kg, at least 0.1 mg/kg, at least 0.5 mg/kg, at least 1.0 mg/kg, at least 2.0 mg/kg, at least 3.0 mg/kg, at least 4.0 mg/kg, at least 5.0 mg/kg, at least 6.0 mg/kg, at least 7.0 mg/kg, at least 8.0 mg/kg, at least 9.0 mg/kg, at least 10 mg/kg, at least 15 mg/kg, at least 20 mg/kg, at least 25 mg/kg, at least 30 mg/kg, at least 35 mg/kg, at least 40 mg/kg, at least 45 mg/kg, at least 50 mg/kg, at least 55 mg/kg, at least 60 mg/kg, at least 65 mg/kg, at least 70 mg/kg, at least 75 mg/kg, at least 80 mg/kg, at least 85 mg/kg, at least 90 mg/kg, at least 95 mg/kg, or at least 100 mg/kg body weight is administered in a single dose. In some embodiments, the compounds of the invention (e.g., a compound of Formula (A), such as any of Formulae (I)-(VII) or any one of Compounds 1-63) are administered to a subject such that a total amount of at least 0.1 mg, at least 0.5 mg, at least 1.0 mg, at least 2.0 mg, at least 3.0 mg, at least 4.0 mg, at least 5.0 mg, at least 6.0 mg, at least 7.0 mg, at least 8.0 mg, at least 9.0 mg, at least 10 mg, at least 1.5 mg, at least 20 mg, at least 25 mg, at least 30 mg, at least 35 mg, at least 40 mg, at least 45 mg, at least 50 mg, at least 55 mg, at least 60 mg, at least 65 mg, at least 70 mg, at least 75 mg, at least 80 mg, at least 85 mg, at least 90 mg, at least 95 mg or at least 100 mg mRNA is administered in one or more doses. 
     EXAMPLES 
     While certain compounds, compositions and methods of the present invention have been described with specificity in accordance with certain embodiments, the following examples serve only to illustrate the compounds of the invention and are not intended to limit the same. 
     Example 1 
     Synthesis of Cationic Lipids 
     In embodiments, a cationic lipid described herein can be prepared by conjugating a dithiol with a carboxylic acid under suitable conditions. Exemplary carboxylic acids are described in Table A, and exemplary dithiols are described in Table B. Accordingly, suitable cationic lipids include those resulting from any combination of the precursors described in Table A and Table B. 
     
       
         
           
               
             
               
                 TABLE A 
               
             
            
               
                   
               
               
                 Carboxylic Acids 
               
            
           
           
               
               
               
            
               
                   
                 Carboxylic Acid 
                 Structure 
               
               
                   
                   
               
               
                   
                 A1 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 A2 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 A3 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 A4 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 A5 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 A6 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 A7 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 A8 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 A9 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE B 
               
             
            
               
                   
               
               
                 Dithiols 
               
            
           
           
               
               
               
            
               
                 Dithiol 
                 Name 
                 Structure 
               
               
                   
               
               
                 B1 
                 1,2-ethanedithiol 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                 B2 
                 1,4-butanedithiol 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                 B3 
                 2,3-butanedithiol 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                 B4 
                 2-mercaptoethyl sulfide 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                 B5 
                 3,6-dioxa-1,8-octane-dithiol 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                 B6 
                 1,3-propanedithiol 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                 B7 
                 1,1-ethanedithiol 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
            
           
         
       
     
     Synthesis of Protected Carboxylic Acid Reagents: 
     Protected carboxylic acids can be prepared as illustrated in Scheme A. Conjugation of these protected carboxylic acids with dithiols and subsequent deprotection can afford the cationic lipids described herein. 
     
       
         
         
             
             
         
       
     
     Example 2 
     Synthesis of Lipid Nanoparticle Formulations 
     In embodiments, cationic lipids described herein can be used in the preparation of lipid nanoparticles according to methods known in the art. For example, suitable methods include methods described in International Publication No. WO 2018/089801, which is hereby incorporated by reference in its entirety. 
     Example 3 
     In Vivo Expression of hEPO after IM injection in BALB/c Mice 
     Lipid nanoparticle formulations comprising human erythropoietin (hEPO) mRNA, Cationic Lipid, DMG-PEG2000, Cholesterol and DOPE were administered intramuscularly to study mRNA delivery and resultant hEPO expression. Male BALB/c mice at 6-8 weeks old are given a single injection of the LNP formulations into the gastrocnemius muscle at a dosage level of 0.1 ug. Blood samples were collected at 6 hours post-dose, hEPO protein expression levels were measured in the sera samples by ELISA and presented in  FIG. 1 . These studies show that the cationic lipids described herein are highly effective at delivery mRNA in vivo, resulting in high expression of the protein or polypeptide encoded by the delivered mRNA. 
     From the foregoing description, one skilled in the art can easily ascertain the essential characteristics of this invention, and without departing from the spirit and scope thereof, can make various changes and modifications of the invention to adapt it to various usages and conditions. 
     All references, patents or applications, U.S. or foreign, cited in the application are hereby incorporated by reference as if written herein in their entireties. Where any inconsistencies arise, material literally disclosed herein controls.