Navigation Links
Sangamo BioSciences Announces Nature Biotechnology Study Demonstrating the Use of Zinc Finger Nucleases to Generate HIV Resistant T Cells
Date:6/30/2008

Preclinical Animal Data Demonstrates Promising Therapeutic Strategy for

HIV/AIDS

RICHMOND, Calif., June 30 /PRNewswire-FirstCall/ -- Sangamo BioSciences, Inc. (Nasdaq: SGMO) announced today the publication of data demonstrating that human immune system cells (CD4 T-cells) can be made resistant to HIV infection by treatment with zinc finger DNA-binding protein nucleases (ZFN(TM)). The data suggest that the ZFN approach, which results in the permanent modification of the CCR5 gene encoding an important receptor for HIV infection, is a promising strategy for the treatment of HIV/AIDS.

The work, which was carried out in the laboratory of Carl June, M.D., Director of Translational Research at the Abramson Family Cancer Research Institute at the University of Pennsylvania School of Medicine, in collaboration with Sangamo scientists, was published as an Advance Online Publication in Nature Biotechnology (http://www.nature.com/nbt/journal/vaop/ncurrent/abs/nbt1410.html).

"A ZFN approach represents the 'next generation' of HIV-entry blocking agents and a potentially promising class of anti-HIV compounds," said, Dr. June who is the senior author of the study. "These proof of principle data, together with experience from individuals that carry a natural mutation in their CCR5 gene suggest that permanent 'knock-out' of the of CCR5 gene is important and clinically relevant for long-term resistance to HIV infection and, we believe, may prove to be more effective than temporary 'knock down' approaches based on small molecule inhibitors, antibodies, antisense or RNAi."

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. 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.

"The data described in this paper are an important demonstration of the potential therapeutic properties of our product," commented Dale Ando, M.D., Sangamo's vice president of therapeutic development and chief medical officer. "We have demonstrated that a single treatment with our CCR5-specific ZFNs generates a population of HIV-resistant human T-cells similar to the situation in individuals carrying the natural CCR5-delta32 mutation. ZFN-modification of these cells is permanent and makes them resistant to HIV. The modified cells preferentially survive and expand in an animal after HIV infection, providing a reservoir of healthy and uninfectable immune cells. Furthermore, we observed that animals given the ZFN-modified cells had increased numbers of CD4 cells and substantially lower levels of HIV in their blood compared to animals given non-modified cells demonstrating statistically significant protection from the virus. In an HIV-infected patient, such modified cells could be available as a protected reservoir within the immune system to fight both opportunistic infections and HIV itself."

Several major pharmaceutical companies have initiated programs to develop small molecule or monoclonal antibody approaches to block the binding of HIV to CCR5. However, a small molecule or antibody approach requires the constant presence of a sufficiently high concentration of these drugs or antibody to block therapeutically relevant numbers of the CCR5 protein, which is present in thousands of copies on the surface of each T-cell and other tissues in the body. One such drug has been approved by the US Food and Drug Administration with a "black box" warning, the strongest for prescription drugs, concerning the risk of liver toxicity and the possibility of heart attacks.

Sangamo's ZFN technology represents a means of potentially circumventing these limitations or risks by specifically modifying only CD4 T-cells, the principal target of HIV pathology, in a one-time exposure of the cells to ZFNs. This results in permanent modification of the CCR5 protein such that HIV cannot enter and infect the cells. This approach could potentially enable the generation of a reservoir of protected CD4 T-cells that are available to fight the opportunistic infections that are characteristic of AIDS as well as HIV itself. Sangamo expects to initiate a clinical trial to evaluate this approach by the end of the year.

Data Reported in the Nature Biotechnology Paper

The reported results demonstrate that a one-time exposure to CCR5-specific ZFNs resulted in the generation of an HIV-resistant population of human primary T-cells by the permanent genetic modification of the CCR5 gene. These ZFN-modified CD4 T-cells expanded stably in HIV-infected cultures for several weeks and appeared to behave identically to untreated T-cells except that they were resistant to infection by HIV. ZFN treated primary CD4 T-cells and transformed CD4 cell lines resisted infection with R5-tropic HIV (virus that uses the CCR5 co-receptor to enter cells), resulting in enrichment of ZFN- generated CCR5-disrupted cells in the population upon long-term exposure to virus (>50 days). Importantly, in the presence of HIV, ZFN-modified CD4 T- cells also preferentially expanded in a mouse model. The modified cells were infused into mice that lack a normal immune system and thus do not reject human cells. After 33 days, the mice were sacrificed and 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 greater than two to three fold higher in mice in the presence of HIV infection (p=0.008). In a second experiment it was determined that 50 days after infection, mice given the ZFN- modified cells had increased numbers of CD4 cells and a statistically significant reduction in viral load in their peripheral blood (P<0.001) compared to mice given control cells. These data suggest that, in the presence of HIV, the ZFN-modified cells have a selective advantage allowing them to evade infection and destruction leaving them able fight 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 co-receptor to gain entry into immune cells. CCR5 is perhaps the most important of the known co- receptors 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 results in a truncated CCR5 protein which cannot be used by HIV as a co-receptor. 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 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 ALS, cancer, HIV/AIDS, neuropathic pain, nerve regeneration, Parkinson's 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 gene modification. Sangamo has established strategic partnerships with companies outside of the human therapeutic space including Dow AgroSciences, Sigma-Aldrich Corporation and several companies applying 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 technology platform, the therapeutic potential of ZFNs for the treatment of HIV/AIDS, strategic partnerships with collaborators 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 Quarterly Report on Form 10-Q. Sangamo BioSciences, Inc. assumes no obligation to update the forward-looking information contained in this press release.


'/>"/>
SOURCE Sangamo BioSciences, Inc.
Copyright©2008 PR Newswire.
All rights reserved

Related medicine technology :

1. Sangamo BioSciences Announces Presentation of Phase 1b ZFP Therapeutic Data at American Diabetes Association Meeting
2. Sangamo BioSciences Provides Update on Diabetic Neuropathy Clinical Programs
3. Sangamo BioSciences Announces Presentation of Data on ZFP Therapeutic for Glioblastoma at American Association for Cancer Research (AACR) Meeting
4. Sangamo BioSciences and Sigma-Aldrich Announce Publication of Study Demonstrating Zinc Finger Technology for Rapid Generation of Knock-Out Cell Lines
5. Sangamo BioSciences Reports 2007 Fourth Quarter and Year-End Financial Results
6. Sangamo BioSciences Announces Completion of Enrollment of Phase 2 Clinical Trial of ZFP Therapeutic for Diabetic Neuropathy
7. Sangamo BioSciences and Sigma-Aldrich Announce Nature Biotechnology Study Demonstrating Zinc Finger Technology for Modification of Human Stem Cells
8. Ardea Biosciences Reports Additional Positive Phase 2a Results for Lead HIV Candidate, RDEA806, Demonstrating Up to 1.9 Log Reduction in Plasma Viral Load with Once-Daily Dosing
9. Pressure BioSciences, Inc. Announces $850,000 NIH SBIR Phase II Award for the Development of a New PCT-dependent System for Improved Biomarker Discovery, Diagnostics, and Drug Discovery
10. Neurocrine Biosciences Completes Petal Study Treatment Phase for Endometriosis
11. Regado Biosciences Announces Publication in Circulation of Clinical Trial Results of REG1 Anticoagulation System
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:3/24/2017)... India , March 24, 2017 Abdominal Aortic Aneurysm Repair ... million by 2022, Globally, registering a CAGR of 5.1% from 2016 to 2022. The ... projected to dominate the market during the study period. ... ... ...
(Date:3/24/2017)... , March 24, 2017 New England Pediatric ... of an award including funding and in-kind service towards ... technology.  "Making blood draws less traumatic ... their whole hospital experience better.  We,re looking forward to ... can help improve care for the kids we treat," ...
(Date:3/24/2017)... 2017 Research and Markets has announced the addition ... Demand Forecast to 2022" report to their offering. ... The global wound care market was worth ... CAGR of 6.7% during 2016-2022 Among the various wound care ... in the global market in 2015. Among the various applications, surgical wound ...
Breaking Medicine Technology:
(Date:3/27/2017)... ... March 27, 2017 , ... M&S ... Certificate of Conformity for the Smart System® 20/20. CE Certification builds upon M&S's ... standards and specifications such as ANSI, ISO and proven test methods used in ...
(Date:3/27/2017)... PA (PRWEB) , ... March 27, 2017 , ... ... business simulation -centric training, today announced the launch of a new research ... strategy, having the skills needed to execute that strategy, and the actual success ...
(Date:3/27/2017)... ... March 27, 2017 , ... According to the American Cancer ... stages, is more than 95%. Once the cancer spreads to other organs, bones, or ... find out how to avoid this latter group, tune in to Lifestyle Magazine ...
(Date:3/27/2017)... Texas (PRWEB) , ... March 27, 2017 , ... ... at the GTEC Orange facility from 8:00am-10:00am on Monday, April 3rd to commemorate ... and will be an opportunity for area-residents to celebrate two great years while ...
(Date:3/25/2017)... PA (PRWEB) , ... March 25, 2017 , ... Getting ... as a public relations partner. , All through the year, Garden Media aims ... press releases, working with key influencers and pitching client’s key messages to ...
Breaking Medicine News(10 mins):