A recombinant viral vector for integrating a transgene into a target integration site in the genome of the cell, comprising: a polynucleotide cassette comprising a first nucleic acid sequence and a second nucleic acid sequence, wherein the first nucleic acid sequence comprises the transgene; and the second nucleic acid sequence is positioned 5' or 3' to the first nucleic acid sequence and promotes the production of two independent gene products upon integration into the target integration site in the genome of the cell; a third nucleic acid sequence positioned 5' to the polynucleotide cassette and comprising sequence that is substantially homologous to genomic sequence 5' of the target integration site in the genome of the cell; and a fourth nucleic acid sequence positioned 3' of the polynucleotide cassette and comprising sequence that is substantially homologous to genomic sequence 3' of the target integration site in the genome of the cell, wherein the viral vector is an rAAV vector; wherein the nucleic acid sequence that promotes the production of two independent gene products at the target integration site is selected from: a sequence that encodes a 2A peptide; an IRES; an intein; a recognition sequence for a site specific protease; a sequence that encodes a cleavable linker that is cleaved as part of the coagulation cascade; a sequence that encodes a factor XI cleavage site; and an intronic splice donor/splice acceptor sequence; and wherein the transgene encodes a protein selected from the group consisting of low-density lipoprotein receptor, purine nucleoside phosphorylase, sphingomyelinase, glucocerebrosidase, CD-18, ornithine transcarbamylase, argininosuccinate synthetase, phenylalanine hydroxylase, branched-chain α-ketoacid dehydrogenase, fumarylacetoacetate hydrolase, glucose 6-phosphatase, α-L-fucosidase, β-glucuronidase, α-L-iduronidase, galactose 1-phosphate uridyltransferase; a BCKDH complex protein (E1a, E1b and E2 subunits); Methylmalonyl-CoA Mutase; Propionyl-CoA Carboxylase (Alpha and Beta subunits); Isovaleryl CoA dehydrogenase; HADHA; HADHB; LCHAD; ACADM; ACADVL; G6PC (GSD1a); G6PT1(GSD1b); and SLC17A3; or wherein the transgene encodes a chimeric polypeptide, comprising an immunoglobulin domain and an immune effector domain, specific for a pathogen selected from: human immunodeficiency virus, influenza virus, respiratory syncytial virus, hepatitis C virus, a plasmodium, plasmodium falciparum, plasmodium malariae, a fungus, and a bacterium; and wherein the target integration site is in the albumin gene. a polynucleotide cassette comprising a first nucleic acid sequence and a second nucleic acid sequence, wherein the first nucleic acid sequence comprises the transgene; and the second nucleic acid sequence is positioned 5' or 3' to the first nucleic acid sequence and promotes the production of two independent gene products upon integration into the target integration site in the genome of the cell; a third nucleic acid sequence positioned 5' to the polynucleotide cassette and comprising sequence that is substantially homologous to genomic sequence 5' of the target integration site in the genome of the cell; and a fourth nucleic acid sequence positioned 3' of the polynucleotide cassette and comprising sequence that is substantially homologous to genomic sequence 3' of the target integration site in the genome of the cell, wherein the viral vector is an rAAV vector; wherein the nucleic acid sequence that promotes the production of two independent gene products at the target integration site is selected from: a sequence that encodes a 2A peptide; an IRES; an intein; a recognition sequence for a site specific protease; a sequence that encodes a cleavable linker that is cleaved as part of the coagulation cascade; a sequence that encodes a factor XI cleavage site; and an intronic splice donor/splice acceptor sequence; and wherein the transgene encodes a protein selected from the group consisting of low-density lipoprotein receptor, purine nucleoside phosphorylase, sphingomyelinase, glucocerebrosidase, CD-18, ornithine transcarbamylase, argininosuccinate synthetase, phenylalanine hydroxylase, branched-chain α-ketoacid dehydrogenase, fumarylacetoacetate hydrolase, glucose 6-phosphatase, α-L-fucosidase, β-glucuronidase, α-L-iduronidase, galactose 1-phosphate uridyltransferase; a BCKDH complex protein (E1a, E1b and E2 subunits); Methylmalonyl-CoA Mutase; Propionyl-CoA Carboxylase (Alpha and Beta subunits); Isovaleryl CoA dehydrogenase; HADHA; HADHB; LCHAD; ACADM; ACADVL; G6PC (GSD1a); G6PT1(GSD1b); and SLC17A3; or wherein the transgene encodes a chimeric polypeptide, comprising an immunoglobulin domain and an immune effector domain, specific for a pathogen selected from: human immunodeficiency virus, influenza virus, respiratory syncytial virus, hepatitis C virus, a plasmodium, plasmodium falciparum, plasmodium malariae, a fungus, and a bacterium; and wherein the target integration site is in the albumin gene.