GENE THERAPY BY SMALL FRAGMENT HOMOLOGOUS REPLACEMENT

BACKGROUND:

Gene therapy has received much attention and focus in recent years as a means of treating human genetic diseases including cystic fibrosis, muscular dystrophy and sickle cell anemia. Generally, a normal gene is inserted randomly into the genome of target cells to complement the non-functional gene. Current gene delivery methods involve the introduction of DNA directly into a patient, including the use of viral vectors.

However, there are several drawbacks to these methods. Activation of the immune response is a potential concern, especially with viral vectors. In addition, non-specific insertion of functional genes can result in random or inappropriate expression of the target protein, which could be toxic or tumorigenic. While replacement of defective genes through homologous recombination would address the specificity concern, methods using homologous recombination have been limited in use due to their low efficiency.

UCSF investigators have discovered a process that permits defective genetic sequences to be replaced with greater efficiency and potentially fewer side effects. The key 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.

ADVANTAGES:

• Elimination of potential mutational events associated with random insertion of new DNA.
• Repaired gene placed under regulation of endogenous promoter, ensuring appropriate expression and avoiding potential toxicity of over-expression.
• Elimination of the immune response problem associated with adenovirus vector.
  

INTELLECTUAL PROPERTY:

UCSF has two issued patents on this targeted gene replacement technique:
US Patent No. 6,010,908
US Patent No. 7,217,571

Related case: SF2001-C07, US Patent No. 6,916,611

If you would like to receive further information about this technology and potential licensing opportunities, please contact:

Eileen Lee, Ph.D.
Licensing Associate
Phone: (415) 353-4664
Fax: (415) 348-1579
eileen.lee@ucsf.edu
Office of Technology Management
Reference: OTM Case #SF1992-A70