The Gene Therapy Research Program is focused on the development of gene therapy and genetic engineering technologies for the application to cancer, transplantation, and regenerative medicine.

The main focus is cancer gene therapy. It is a promising new approach in which genes delivered directly to cancer cells will serve as the blueprint for therapeutic proteins that kill the cells from within or will provoke an immune response so that the body rejects the cells. While this method promises to be more effective with fewer side effects than current chemotherapy, the efficiency of delivering genes has proven to be a major obstacle to its success. Many strategies for gene therapy have involved the use of certain viruses as vehicles ("vectors") for gene delivery, because viruses have evolved efficient ways to insert their genes into human cells. By removing the viral genes that naturally allowed the virus to spread from cell to cell, these vectors were made safer; however, over the last decade, it has been found that the efficiency of these disabled viruses in infecting tumors and delivering genes is too low to be therapeutically useful.

Dr. Noriyuki Kasahara was one of the first to demonstrate that by making retrovirus vectors that are less disabled and hence can take advantage of the natural process of virus replication and spread from cell to cell, their efficiency is greatly improved for gene delivery targeted to human cancers. His group is now leading a consortium that is funded by a multi-institutional U01 award from the NIH; it includes collaborating groups at UC San Francisco, the University of Southern California, the National Gene Vector Biorepository, and biotech partner Tocagen Inc. in the development of this tumor-selective replication-competent retrovirus (RCR) vector system for clinical use. The Investigational New Drug (IND) application to conduct a first-in-man Phase I clinical trial for the RCR vector-mediated suicide gene therapy in brain tumor patients wasapproved by the Food and Drug Administration (FDA), and this trial was initiated at UCLA in August 2010. Read Fall 2012 update on "Dr. Kasahara's group is now leading a consortium that has initiated a first-in-human clinical trial to test this novel gene therapy technology in brain cancer patients"

Other projects ongoing in the Gene Therapy Research Program focus on emulating and adapting the mechanisms used by tumors to evade or suppress the immune system and applying them toward achieving long-term graft survival in cellular transplantation. Dr. Kasahara's group was among the first to demonstrate that this capability can be achieved by using the gene transfer of small interfering RNA (siRNA) to silence specific tissue antigens (HLA) and thereby enhance the histocompatibility of donor cells to be transplanted into HLA-mismatched recipients. Furthermore, it is increasingly apparent that human adult and embryonic stem-cell-derived tissues, which do not initially express HLA, subsequently increase their levels of HLA expression as they differentiate into mature tissues. Hence, this strategy also has significant implications for regenerative medicine: Any non-autologous adult stem-cell-derived tissues and every embryonic stem-cell-derived tissue will eventually encounter the same problems of immune rejection that have long confronted the field of adult organ transplantation, and it is hoped that this strategy may represent an effective and fundamentally different approach to overcoming such problems by genetically modifying the donor-derived graft cells to evade the recipient's immune system instead of immunosuppressing the recipient host.

Learn more about our team

Noriyuki Kasahara, MD, PhDDirector, JCCC Vector Shared Resource & CURE Vector Core Facility Professor, Departments of Medicine and Molecular & Medical Pharmacology

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UCLA | Gene Research Therapy, Noriyuki Kasahara MD PhD ...

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