METHODS FOR TARGETED INSERTION OF DNA IN GENES

1 - 17 . (canceled)

18 . A eukaryotic cell comprising a genome with a transgene, wherein the transgene comprises 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 from Factor VIII, Factor IX, GBA, GLA, IDS, IDUA, ATXN3, USH2A, G6PT or the corresponding gene for alpha-1 antitrypsin deficiency,

wherein the transgene is equal to or less than 4.7 kb,

wherein the transgene is flanked by intron sequence of an endogenous gene within said genome, and wherein the transgene is operably linked to the promoter of the endogenous gene.

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

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

21 . A method of detecting a transgene within an intron of the genome of a eukaryotic cell, wherein the method comprises:

a. providing the eukaryotic cell of claim 1 ,

b. isolating genomic DNA from said eukaryotic cell, and

c. detecting the transgene using PCR.

22 . The method of claim 21 , wherein the first terminator is selected from an SV40 poly(A) or BGH poly(A).

23 . The method of claim 22 , wherein the second terminator is selected from an SV40 poly(A) or BGH poly(A).