THERAPEUTIC GENE TARGETING

Gene targeting is the use of homologous recombination to make defined alterations to the genome. One of the possible outcomes of gene target ing is the accurate correction of genetic defects, and this would make it the ideal method of gene therapy for single gene disorders. While gene targeting has been achieved both in human cell lines and in nontr ansformed, primary human cells its low efficiency has been a major lim itation to its therapeutic potential. Gene therapy by in vivo gene tar geting is therefore impractical without dramatic improvements in targe ting efficiency. Ex vivo approaches might more realistically be consid ered, but would benefit from progress in the isolation and growth of s omatic stem cells and improvements in targeting efficiency. We provide here a brief review of the challenges of gene therapy by gene targeti ng. This is followed by a critical overview of recent developments in gene targeting techniques, and in our understanding of the underlying processes of homologous and nonhomologous recombination.