Sangamo BioSciences Presents First ZFP Therapeutic Data Demonstrating in Vivo Protection Against HIV
- Category: DNA RNA and Cells
- Published on Friday, 08 June 2007 04:00
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RICHMOND, CA, USA | June 6, 2007 | Sangamo BioSciences, Inc. (Nasdaq: SGMO) announced the presentation of data from its program to develop a zinc finger DNA-binding protein (ZFP) Therapeutic(TM) for HIV/AIDS that demonstrate that ZFN-modified human T-cells are protected from HIV infection and have a selective survival advantage in a mouse model of HIV challenge. In the second half of 2007, Sangamo expects to initiate a Phase 1 clinical trial to test this HIV ZFP Therapeutic, working with Dr. Carl June, Director of Translational Research at the Abramson Family Cancer Research Institute and collaborators at the University of Pennsylvania.
Sangamo's ZFP nuclease (ZFN(TM)) technology can be used to make human primary T-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. Individuals have been identified who carry a natural mutation of the CCR5 gene, CCR5-delta32, which confers resistance to HIV infection. HIV infection kills or impairs cells of the immune system, progressively destroying the body's ability to fight infections resulting in AIDS (Acquired Immune Deficiency Syndrome). Individuals diagnosed with AIDS are susceptible to life-threatening diseases or opportunistic infections, which are caused by microbes that usually do not cause illness in people with healthy immune systems. Sangamo's initial approach is to modify the CCR5 gene in T-cells to provide patients with a reservoir of ZFN-modified HIV-resistant immune cells that can fight opportunistic infections and the virus itself.
"Scientists from Sangamo Biosciences approached me with an extraordinary proposition," stated Dr. June. "They told me that they had the means to create CD4+ T-cells with permanent modification of the CCR5 gene and a robust resistance to HIV infection. This exciting collaboration, involving my colleagues at the University of Pennsylvania and the team of scientists at Sangamo has rapidly progressed from that idea to data demonstrating that ZFN modified cells are HIV resistant and have a selective survival advantage when reintroduced into an animal. This is consistent with our aim of reconstituting a functional HIV-resistant immune system in patients infected with the virus.
"This is the first presentation of in vivo data from our program to develop a ZFP Therapeutic for the treatment of HIV, and it is significant that these animal data confirm our earlier observations in isolated cells," stated Dale Ando, M.D., Sangamo's vice president of therapeutic development and chief medical officer. "Previously, we had shown that ZFN-modified primary human T-cells are resistant to HIV infection not only surviving continuous exposure to HIV but selectively expanding in cell culture to the point that they represented the vast majority of cells in the population at the end of the experiment. In these more recent data we show that that observation holds true when these HIV-resistant cells are tested in a mouse model of HIV infection and demonstrate that after ZFN-modification the cells are stable and have a selective advantage in the presence of HIV."
In the experiments presented by Dr. June and Sangamo scientist, Michael Holmes, Ph.D., isolated human T-cells were treated with ZFNs specific for CCR5. The modified cells were infused into a mouse model, the NOG mouse, with or without a source of HIV. The NOG mouse lacks an immune system and thus does not reject the human cells. After 33 days, the mice were sacrificed and their blood analyzed for the presence of ZFN-modified cells. Researchers determined that ZFN-modified cells engrafted normally in the mouse and that the proportion of modified cells present at the end of the experiment was statistically significantly higher in mice in the presence of HIV infection (p=0.008). These data suggest that, in the presence of HIV, the ZFN-modified cells have a selective advantage and evade HIV infection and destruction.
"These animal data are very encouraging as we prepare to initiate a Phase 1 clinical trial in HIV/AIDS with this ZFP Therapeutic in the second half of 2007," stated Edward Lanphier, Sangamo's president and CEO. "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 combat opportunistic infections and HIV itself. We believe that using ZFNs to permanently modify the CCR5 gene in T-cells and thus directly block HIV from entering cells may have a number of advantages over the systemic effects of CCR5 antagonists in development."
The data were presented on June 1, 2007 at the 10th Annual Meeting of the American Society of Gene Therapy (ASGT), which was held in Seattle, Washington. In addition to Dr. Holmes' presentation, which was selected for the prestigious Presidential Symposium, Sangamo scientists and collaborators presented data in six oral presentations and three posters describing preclinical data from Sangamo's ZFP Therapeutic programs. These included programs in pain, nerve crush and spinal cord injury, macular degeneration and glioblastoma. In addition, Sangamo sponsored a Symposium chaired by Donald Kohn, M.D., Director, Gene, Immune and Stem Cell Therapy Program at Children's Hospital Los Angeles, which featured the following presentations:
-- ZFPs as Therapeutics - Applications and Advantages of the Technology: Philip Gregory, D. Phil., Vice President, Research, Sangamo BioSciences, Inc.
-- Therapeutic Applications of a ZFP TF activator of VEGF-A: Dale Ando, M.D., CMO and Vice President, Therapeutic Development, Sangamo BioSciences, Inc.
-- ZFN Mediated Disruption of CCR5 to Create CCR5 deficient CD4 Cells for HIV Therapy: Carl June, M.D., Director, Translational Research, Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine
-- Gene Editing & Site-Specific Gene Addition in Human Stem Cells Using ZFN and Integrase-Defective Lentiviral Vectors: Luigi Naldini, M.D., Ph.D., Professor of Cell and Tissue Biology, School of Medicine, Scientific Co director, The San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET)
-- Engineering Cellular Scalpels for Excising Invasive Tumor Cells of Malignant Glioma: Michael Jensen, M.D., Associate Chairman, Division of Cancer Immunotherapeutics and Tumor Immunology, Beckman Research Institute, City of Hope
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 program is currently in Phase 2 clinical trials for evaluation of safety and clinical effect in patients with diabetic neuropathy. Phase 1 clinical trials are ongoing to evaluate a ZFP Therapeutic for peripheral artery disease. Other therapeutic development programs are focused on cancer and HIV/AIDS, neuropathic pain, nerve regeneration, ischemic heart disease 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. For more information about Sangamo, visit the company's web site at http://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.
SOURCE: Sangamo BioSciences, Inc.