The virus used against itself

Jan 19, 2007 11:09 GMT  ·  By

More than twenty years of research have not succeeded in stopping HIV.

Now, researchers believe that gene therapy could hold the infamous virus.

The only obstacle by now is finding an efficient transport system able to transport therapeutic DNA to target cells.

A complex team is exploring a completely new way of manipulating the body's natural defense system. "Rather than focusing on conventional vaccines that boost the immune system, we are experimenting with a way to help the immune system produce antibodies that can neutralize the virus," said Pin Wang of the USC Mork Family Department of Chemical Engineering and Materials Science.

"If we can design a modified virus that will deliver these antibodies to chosen cells, we will be able to insert DNA that will help rather than harm cells."

Viruses were found as efficient carriers that can insert DNA material in the DNA of the host cells.

HIV is hard to detect by the immune system, because it possesses an unusual sugar-coated shield that enables it to avoid detection. "The shield has very few open spaces on its surface, which makes it virtually impossible to penetrate. And because the virus also has an uncanny ability to hide, HIV often goes virtually unnoticed by neutralizing antibodies that are roaming the body in search of foreign invaders", explained Wang.

The team will use HIV's hollow shells as transporters to insert DNA that will stop the infection. An HIV-based "lentiviral vector" (a type of retrovirus) that uses the backbone of a virus to infect both dividing and nondividing cells will be employed as the most suited gene transporters.

The target cells are hematopoietic stem cells, the bone marrow cells that generate immune cells, like B lymphocytes. These cells will be programmed to produce rare antibodies such as B12, 4E10, 2G12 and 2F5. "In laboratory tests, we remove harmful genes coding for the HIV virus and engineer the backbone, or spine, of virus so that it is no longer replicable" he says. "Once manufactured recombinantly, this modified virus - the lentiviral vector -- becomes a natural delivery system that can transport useful genes into cells without causing illness."

Another issue is programming lentiviral transporters to enter only hematopoietic stem cells, in order to get the desired targeted delivery. In two years of research, the team managed to specifically target human B cells in mice. "Possibly the most important implication of the work is that gene therapy could now be carried out as an inexpensive procedure, able to be considered even in the less-developed world," wrote the researchers. "I think we are finally on the right track," Wang says.

"If scientists can find a way to genetically engineer immune cells to neutralize HIV, we may be able to develop immunotherapy for HIV-Infected people, as well as find ways to prevent it all together."