( versary Wang wants to synthetically al...)Researchers Explore the Effect of Engineered Immune Cells on HIV,Health

versary, Wang wants to synthetically alter the HIV viral invaders and use their hollow shells as delivery vehicles to insert DNA that will counteract the infection.

The "Cadillac" of this gene delivery system is an HIV-based "lentiviral vector," a type of retrovirus that uses the backbone of a virus to infect both dividing and nondividing cells. Wang says lentiviral vectors are very efficient delivery vehicles for human cells.

Collaborators on his project are targeting hematopoietic stem cells -- the bone marrow cells that form blood cells – to create B lymphocytes. The researchers want to reprogram these bone marrow cells by adding genes that will instruct the cells to produce rare antibodies such as B12, 4E10, 2G12 and 2F5. Wang says these antibodies are known to neutralize the virus.

"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."

Although the gene delivery technique looks promising, researchers are still working on ways to manipulate these elusive bone marrow cells and get them to generate "designer immune cells." Another problem seems to be making sure lentiviral vectors target only hematopoietic stem cells, and not other types of cells, to achieve the desired targeted delivery.

With a group of USC biomedical engineering students and Caltech biologists, Wang is experimenting with CD20 as a target antigen for human B cells. His strategy, published in the August 1, 2006 issue of Proceedings of the National Academy of Sciences, targets the human B cells only. After two years of experimentation, the team has been able to demonstrate that they can specifically target human B cells in mice.

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