Methods for targeted insertion of DNA in genes

A recombinant nucleic acid comprising,

• (i) a transgene, the transgene comprising from 5′ to 3′ orientation:
• a first splice acceptor, a first coding sequence, a first terminator, a second terminator reverse complement, a second coding sequence reverse complement, and a second splice acceptor reverse complement, wherein the first coding sequence is operably linked to the first splice acceptor and first terminator, and the second coding sequence is operably linked to the second splice acceptor and second terminator,
• wherein the first and second coding sequences differ in nucleic acid sequence but encode the same amino acids, wherein said amino acids encoded by the first and second coding sequences correspond to amino acids encoded by an endogenous gene, and
• wherein the transgene is equal to or less than 4.7 kb, and
• (ii) adeno-associated virus inverted terminal repeats flanking the transgene, and wherein the recombinant nucleic acid is in a circular conformation.