Gene Excision and Replacement

GENE EXCISION AND REPLACEMENT

Diseases at a genetic level can result from several causes, including (1) mutation in a gene, (2) loss of ex-pression of a gene, (3) elevated expression of a gene, or (4) expression of a pathogenic viral or foreign gene. In each case, gene replacement or excision therapy might be desirable. Theoretically, the disease gene could be re-placed through a homologous recombination event. Depending on the design of the replacement gene, it also would be possible to engineer stop codons or non-sense sequences into the internal domains of a gene to ensure loss of protein production. Excision of an entire gene also is feasible. 

This strategy, however, requires ex-tremely efficient and specific homologous recombina-tion events in the target cell population. Such strategies have allowed for the development of knockout animals, but to date have not been practical for human somatic cell gene therapy. Ongoing investigations are exploring the feasibility of inducible vectors, use of the cre-lox sys-tem, or cell type specific promoters to optimize gene ex-pression in target cells.