Sangamo BioSciences, Inc. Says Compound Makes Cells Resistant To HIV
RICHMOND, Calif., Sept. 27 /PRNewswire-FirstCall/ -- Sangamo BioSciences, Inc. announced today data demonstrating that human immune system cells can be made permanently resistant to HIV infection by treatment with zinc finger DNA-binding protein nucleases (ZFN(TM)). Sangamo's ZFNs are designed to permanently modify the DNA sequence encoding CCR5, a co-receptor that enables HIV to enter and infect cells of the immune system. The presentation, entitled, "Towards Gene Knock Out Therapy for AIDS/HIV: Targeted Disruption of CCR5 Using Engineered Zinc Finger Protein Nucleases" is taking place today at the 46th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy in San Francisco.
The presentation is co-authored by Sangamo's collaborators in the laboratory of Dr. Carl June, Director of Translational Research at the Abramson Family Cancer Research Institute at the University of Pennsylvania School of Medicine.
The reported results demonstrate that in T-cell lines and in primary human CD4+ T-cells, administration of Sangamo's CCR5-ZFNs enabled the generation of a population of CCR5-modified, HIV resistant cells. ZFN-modified T-cell lines survived continuous exposure to HIV and expanded to the point that they represented the vast majority of cells in the population at the end of the experiment (70 days). Significant enrichment was also reported for ZFN- modified primary human CD4+ T-cells exposed to HIV. In addition, plasmid DNA plus electroporation and adenoviral vectors were evaluated as modes of delivery of CCR5-specific ZFNs. While both methods support ZFN-mediated CCR5 disruption of T-cells, adenoviral delivery resulted in a ten-fold increase in CCR5-modified cells compared with non-viral methods. Researchers at Sangamo and the University of Pennsylvania are evaluating the long-term consequences and advantages of both delivery methods. Sangamo's clinical goal is to treat T-cells of HIV-infected individuals to generate a reservoir of T-cells that is permanently resistant to HIV infection.
Dale Ando, M.D., Sangamo's vice president of therapeutic development and chief medical officer, commented, "These are very important data, demonstrating that we are able to generate a population of HIV-resistant immune cells similar to the situation in individuals carrying the natural CCR5-delta32 mutation which confers resistance to HIV infection. We believe such a reservoir of healthy and uninfectable T-cells in a patient would be available to fight both opportunistic infections and HIV itself. In addition, we have made significant advances in the production process for this therapeutic approach and determined that delivery of our ZFNs by adenovirus may give us advantages in delivery efficiency and T-cell survival over other delivery methods that we are evaluating."
Dr. Carl June stated, "The positive results being presented at ICAAC continue to strengthen our belief that CCR5-ZFNs are a novel and potentially promising class of anti-HIV compounds. I am greatly encouraged by these findings and look forward to collaborating with Sangamo further to bring this program into the clinic as quickly as possible."
CCR5 is a highly validated therapeutic target for development of drugs to treat HIV. Individuals carrying a naturally occurring mutation of their CCR5 gene, a variant known as CCR5-delta32, have been shown to be resistant to HIV infection. Several major pharmaceutical companies have initiated programs developing small molecule or antibody approaches to block the binding of HIV to CCR5. However, a small molecule or antibody approach to this problem requires the constant presence of a sufficiently high concentration of drug to block therapeutically relevant numbers of the CCR5 protein, which is present in thousands of copies on the surface of each T-cell. The development of several programs to test small molecule antagonists of CCR5 has been halted due to concerns about toxicity of the compounds. In contrast, Sangamo believes that its ZFN technology represents a means of circumventing these limitations. Only brief exposure of immune cells to ZFNs is required for permanent modification of cells' CCR5 protein making them resistant to HIV infection.
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 ischemic heart disease, neuropathic pain, cancer 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 X- linked SCID and hemophilia, 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 research and development of novel ZFP TFs and ZFNs as ZFP Therapeutics, applications of Sangamo's ZFP TF technology platform and clinical trials of ZFP Therapeutics. Actual results may differ materially from these forward-looking statements due to a number of factors, including technological challenges, uncertainties relating to the initiation and completion of stages of ZFP Therapeutic clinical trials, 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/