A composition comprising: i. a nuclease or a vector comprising a nuclease; and ii. one or more vectors comprising a) at least one guide nucleic acid molecule that targets said nuclease to a target nucleic acid of said genome at a target locus; b) a single stranded oligonucleotide or double stranded nucleic acid molecule comprising a heterologous nucleic acid molecule of interest (NOI); c) a first sequence homologous to a first flanking sequence upstream of said target locus; and d) a second sequence comprising a second flanking sequence downstream of said target locus, wherein said first and second flanking sequences comprise about 50 nucleotides or less when said first and second flanking sequence comprise a single stranded oligonucleotide and said first and second flanking sequences comprise about 1000 nucleotides or less when said first and second flanking sequences comprise a double stranded oligonucleotide; for use in a method for treating or preventing a disease by targeted nucleic acid editing in a nonhuman animal genome of a nonhuman animal; the method comprising: injecting the composition into a zygote of said nonhuman animal; wherein said nonhuman animal zygote has been produced by fertilizing a nonhuman animal oocyte with nonhuman animal spermatozoa and comprises said genome of said nonhuman animal; said nonhuman animal having pronuclei that cannot be visually observed by the unaided human eye; wherein said composition is injected into the cytoplasm of said zygote before a single nucleus forms; and wherein said nuclease can introduce a double stranded break at said target locus of said target gene of said animal genome. i. a nuclease or a vector comprising a nuclease; and ii. one or more vectors comprising a) at least one guide nucleic acid molecule that targets said nuclease to a target nucleic acid of said genome at a target locus; b) a single stranded oligonucleotide or double stranded nucleic acid molecule comprising a heterologous nucleic acid molecule of interest (NOI); c) a first sequence homologous to a first flanking sequence upstream of said target locus; and d) a second sequence comprising a second flanking sequence downstream of said target locus, wherein said first and second flanking sequences comprise about 50 nucleotides or less when said first and second flanking sequence comprise a single stranded oligonucleotide and said first and second flanking sequences comprise about 1000 nucleotides or less when said first and second flanking sequences comprise a double stranded oligonucleotide; a) at least one guide nucleic acid molecule that targets said nuclease to a target nucleic acid of said genome at a target locus; b) a single stranded oligonucleotide or double stranded nucleic acid molecule comprising a heterologous nucleic acid molecule of interest (NOI); c) a first sequence homologous to a first flanking sequence upstream of said target locus; and d) a second sequence comprising a second flanking sequence downstream of said target locus, for use in a method for treating or preventing a disease by targeted nucleic acid editing in a nonhuman animal genome of a nonhuman animal; the method comprising: injecting the composition into a zygote of said nonhuman animal; wherein said nonhuman animal zygote has been produced by fertilizing a nonhuman animal oocyte with nonhuman animal spermatozoa and comprises said genome of said nonhuman animal; said nonhuman animal having pronuclei that cannot be visually observed by the unaided human eye; wherein said composition is injected into the cytoplasm of said zygote before a single nucleus forms; and wherein said nuclease can introduce a double stranded break at said target locus of said target gene of said animal genome. <EOS>