METHODS FOR TARGETED INSERTION OF DNA IN GENES

1 - 17 . (canceled)

18 . A eukaryotic cell comprising a linear transgene, the linear 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 terminator is selected from an SV40 poly(A) or BGH poly(A),

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.

19 . The eukaryotic cell of claim 18 , wherein the second terminator is selected from an SV40 poly(A) or BGH poly(A).

20 . The eukaryotic cell of claim 18 , wherein the transgene is harbored on a viral vector.

21 . The eukaryotic cell of claim 20 , wherein the viral vector is selected from the group consisting of an adenovirus vector, an adeno-associated virus vector, and a lentivirus vector.

22 . The eukaryotic cell of claim 21 , wherein the viral vector is an adeno-associated viral vector.

23 . The eukaryotic cell of claim 23 , wherein the transgene does not comprise homology arms.

24 . The eukaryotic cell of claim 18 , wherein the endogenous gene is selected from Factor VIII, Factor IX, GBA, GLA, IDS, IDUA, AXTN3, USH2A or G6PT.

25 . The eukaryotic cell of claim 18 , wherein the endogenous gene is the corresponding endogenous gene for alpha-1 antitrypsin deficiency.