Free Newsletter
Register for our Free Newsletters
Analysis, Inspection and Laboratory
Assisted/Independent Living
Clinical and Nursing Equipment
Design and Manufacture of Medical Equipment
Diagnostics Equipment, Monitoring and Test
Education, Training and Professional Services
Health Education and Patient Management
Health Estates Management
Healthcare Support and Information Services
Hygiene and Infection Control
IT and Communications in Healthcare
Medical Device Technology
Research and Development
Safety and Security
View All
Other Carouselweb publications
Carousel Web
Defense File
New Materials
Pro Health Zone
Pro Health Zone
Pro Security Zone
Web Lec
Pro Engineering Zone

Study shows zinc finger nucleases are able to generate HIV resistant T cells

Sangamo BioSciences : 01 July, 2008  (Company News)
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) has been released.
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, MD, director of translational research at the Abramson Family Cancer Research Institute at the University of Pennsylvania School of Medicine, in collaboration with scientists from Sangamo BioSciences, was published as an Advance Online Publication in Nature Biotechnology.

'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, MD, 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.
Bookmark and Share
Home I Editor's Blog I News by Zone I News by Date I News by Category I Special Reports I Directory I Events I Advertise I Submit Your News I About Us I Guides
   Â© 2012
Netgains Logo