GENE THERAPY BY SMALL FRAGMENT HOMOLOGOUS REPLACEMENT

University of California System: University of California, San Francisco
posted on 01/09/2009

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Current methods of gene delivery used in gene therapy have several drawbacks. For example, the use of viral vectors is associated with activation of the immune response which can reduce the efficiency of gene delivery to the target cell and can cause serious complications for the patient. In addition, non-specific insertion of functional genes can result in random or inappropriate expression of the target protein, and can disrupt the expression of important tumor suppressor genes, with toxic or tumorigenic results.
Replacement of defective genes by homologous recombination would eliminate concerns associated with the use of viral vectors and the nonspecific insertion of genes into the genome.
UCSF investigators have discovered a process that permits defective genetic sequences to be replaced with greater efficiency and potentially fewer side effects. The process, small fragment homologous replacement (SFHR), allows genes to be repaired in a site specific fashion and does not require the insertion of new genetic material into the genome. Thus, the SFHR approach should be applicable to a wide variety of gene therapy applications requiring the repair of specific mutations in DNA sequence. Furthermore, assay methods have been developed to monitor and quantify gene targeting frequency and to differentiate between cells carrying modified and unmodified DNA.