RICHMOND, Calif., Feb. 9 /PRNewswire-FirstCall/ -- Sangamo BioSciences, Inc. today announced that data from its program to develop a zinc finger DNA-binding protein (ZFP) treatment for HIV/AIDS were presented in an oral session at the 13th Conference on Retroviruses and Opportunistic Infections (CROI) held in Denver this week. The data demonstrate that Sangamo’s ZFP nuclease (ZFN(TM)) technology can be used to make cells resistant to HIV infection by permanently modifying the DNA sequence encoding CCR5, an essential co-receptor for the entry of HIV into immune cells. In the second half of 2006, Sangamo intends to initiate a Phase 1 clinical trial to test this HIV ZFP Therapeutic, working in close collaboration with Dr. Carl June of the University of Pennsylvania School of Medicine.
According to Dale Ando, M.D., Sangamo’s vice president of therapeutic development and chief medical officer. “The research findings presented at CROI demonstrated permanent ZFN-mediated modification of the CCR5 gene in primary and transformed human T-cells and in model systems of HIV infection. ZFN-modified cells were shown to be resistant to HIV infection. Moreover, the cells were able to grow in culture under conditions in which they were exposed to the virus for prolonged periods. When CCR5 expression was experimentally restored to the ZFN-modified cells, HIV was once again able to infect them demonstrating the selectivity of the approach.”
“Presentation of data in an oral session at a meeting of the world’s leading HIV researchers is another significant validation of our approach to treating HIV infection,” stated Edward Lanphier, Sangamo’s president and CEO. “Based on the results presented at CROI, we believe that using ZFNs to permanently modify the CCR5 gene in T-cells and thus directly block the expression of the protein on the surface of these cells may have a number of advantages over the systemic effects of other drugs in development.”
Several major pharmaceutical companies have initiated programs developing small molecule or antibody approaches to block the binding of HIV to CCR5. Unfortunately, these approaches require the constant presence of antagonist in high enough concentrations to block therapeutically relevant numbers of the CCR5 protein, which is present in thousands of copies on the surface of each T-cell. In contrast, brief exposure of T-cells to Sangamo’s ZFNs has been shown to result in permanent modification of the CCR5 gene and consequent alteration of the CCR5 protein.
Dr. June, Director of Translational Research at the Abramson Family Cancer Research Institute at the University of Pennsylvania School of Medicine, stated, “The findings presented at CROI are encouraging and demonstrate the promise of this new approach. By administering ZFNs to patients’ T-cells, the goal is to provide HIV-infected individuals with a reservoir of healthy and uninfectable immune cells that would be available to fight both opportunistic infections and HIV itself.”
About HIV/AIDS and CCR5
HIV stands for Human Immunodeficiency Virus. HIV infection kills or impairs cells of the immune system, progressively destroying the body’s ability to fight infections and certain cancers resulting in AIDS (Acquired Immune Deficiency Syndrome). Individuals diagnosed with AIDS are susceptible to life-threatening diseases called opportunistic infections, which are caused by microbes that usually do not cause illness in healthy people. According to Worldaidsday.org, over 3 million people were infected with HIV in 2005. There are now over 40 million people living with HIV and AIDS worldwide.
CCR5 is the chemokine receptor that HIV uses as a coreceptor to gain entry into immune cells. CCR5 is perhaps the most important of the known coreceptors for HIV, since the most commonly transmitted strains of HIV are strains that bind to CCR5 -- so-called “R5" strains. A small fraction of the population carries a mutation in their CCR5 gene, called the delta32 mutation. This mutated version of the gene produces malformed CCR5 proteins, which cannot be used by HIV as a coreceptor. Individuals that have mutant delta 32 versions of both of their CCR5 genes are resistant to infection by R5 HIV strains.
About Sangamo
Sangamo BioSciences, Inc. is focused on the research and development of novel DNA-binding proteins for therapeutic gene regulation and modification. The most advanced ZFP Therapeutic(TM) development programs are currently in Phase 1 clinical trials for evaluation of safety in patients with diabetic neuropathy and peripheral artery disease. Other therapeutic development programs are focused on macular degeneration, ischemic heart disease, congestive heart failure, neuropathic pain, and infectious and monogenic diseases. Sangamo’s core competencies enable the engineering of a class of DNA-binding proteins known as zinc finger DNA-binding proteins (ZFPs). By engineering ZFPs that recognize a specific DNA sequence Sangamo has created ZFP transcription factors (ZFP TF(TM)) that can control gene expression and, consequently, cell function. Sangamo is also developing sequence-specific ZFP Nucleases (ZFN(TM)) for therapeutic gene modification as a treatment for a variety of monogenic diseases, such as sickle cell anemia, and for infectious diseases, such as HIV. Sangamo has established several Enabling Technology Agreements with companies to apply its ZFP Technology to enhance the production of protein pharmaceuticals. Research at Sangamo is partially funded by an Advanced Technology Program (ATP) grant awarded by the National Institute of Standards and Technology (NIST). For more information about Sangamo, visit the company’s web site at www.sangamo.com.
This press release may contain forward-looking statements based on Sangamo’s current expectations. These forward-looking statements include, without limitation, references to the effectiveness of using ZFNs to treat patients with HIV, the initiation of clinical trials, research and development of novel ZFP TFs and ZFNs and therapeutic applications of Sangamo’s ZFP technology platform. Actual results may differ materially from these forward-looking statements due to a number of factors, including uncertainties relating to the further study and development of our ZFN technology, initiation of clinical trials of ZFP Therapeutics, whether such clinical trials will validate and support tolerability and efficacy of ZFP Therapeutics, the effectiveness of our research and development of novel ZFP TFs and ZFNs and therapeutic applications of Sangamo’s ZFP technology platform, technological challenges, Sangamo’s ability to develop commercially viable products and technological developments by our competitors. See the company’s SEC filings, and in particular, the risk factors described in the company’s Annual Report on Form 10-K and its most recent 10-Q. Sangamo BioSciences, Inc. assumes no obligation to update the forward-looking information contained in this press release.
Sangamo BioSciences, Inc.
CONTACT: Elizabeth Wolffe, Ph.D., of Sangamo BioSciences, Inc.,+1-510-970-6000, ext. 271, or ewolffe@sangamo.com; or media, Justin Jacksonof Burns McClellan, Inc, +1-212-213-0006, or jjackson@burnsmc.com, forSangamo BioSciences, Inc.
Web site: http://www.sangamo.com//
