Homologous recombination based gene therapy

Background/Aims: Most of the current expression vector based gene therapy p rotocols fail to achieve clinically significant transgene expression requir ed for treating genetic diseases. Homologous recombination, initially consi dered to be of limited use for gene therapy because of its low frequency in mammalian cells, has recently emerged as a potential strategy for developi ng gene therapy. Methods: Six recent studies of homologous recombination in mammalian cells are reviewed. Different approaches have been used in these studies including RNA/DNA chimeric oligonucleotides, small or large homolo gous DNA fragments, or adeno-associated viral vectors, Results: Most of the se studies show a reasonable frequency of homologous recombination which wa rrants further in vivo testing, Conclusions: Homologous recombination based gene therapy has the potential to develop into a powerful therapeutic moda lity for genetic diseases. It can offer permanent expression and normal reg ulation of corrected genes in appropriate cells or organs and probably can be used for treating dominantly inherited diseases such as polycystic kidne y disease.