Can engineered immune cells stop AIDS?

January 18, 2007

Twenty years after its introduction, gene therapy still holds great promise as a way to harness the insidious power of viruses such as human immunodeficiency syndrome (HIV). But scientists have yet to solve a vexing problem: developing an efficient transport system that is capable of delivering therapeutic payloads to specific cells.

As challenging as the problem has been, researchers in the USC Viterbi School of Engineering may be turning a corner. With support from a $13.9 million grant from the Bill and Melinda Gates Foundation, a multi-institutional team of scientists, including Pin Wang of the USC Mork Family Department of Chemical Engineering and Materials Science, 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," says Wang. "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 are efficient carriers or transport vehicles in the body because they are naturally able to penetrate cells, inserting the genetic material they contain into their new host. By itself, a virus cannot reproduce; it must infect a cell and take control of the host's machinery to make copies.

HIV also possesses an unusual structure and a keen ability to hide from antibodies in a sugar-coated shield. The shield has very few open spaces on its surface, Wang says, 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.

Faced with such a clever adversary, Wang wants to synthetically alter the HIV 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.

"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," Wang and his coauthors wrote.

That's good news for the World Aids Foundation, which announced on World AIDS Day (Dec. 1, 2006) that the disease is on the rise again. More than 39 million people around the world are now infected with HIV, the foundation reported.

"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."

Source: University of Southern California

Explore further: Nanoparticle vaccine offers universal protection against influenza A viruses, study finds

Related Stories

Nanoparticle vaccine offers universal protection against influenza A viruses, study finds

January 24, 2018
Researchers have developed a universal vaccine to combat influenza A viruses that produces long-lasting immunity in mice and protects them against the limitations of seasonal flu vaccines, according to a study led by Georgia ...

Scientists show how memory B cells stay 'in class' to fight different infections

May 7, 2012
Scientists at The Scripps Research Institute have made an important discovery about the internal programming of B cells, the immune cells that make antibodies against infections. The finding opens the way for the development ...

Speeding up bone growth by manipulating stem cells

June 25, 2012
If you break a bone, you know you'll end up in a cast for weeks. But what if the time it took to heal a break could be cut in half? Or cut to just a tenth of the time it takes now? Qian Wang, a chemistry professor at the ...

Researchers pinpoint peptide that blocks hepatitis C virus entry

August 1, 2012
(Medical Xpress) -- Researchers at the University of Pittsburgh’s Graduate School of Public Health (GSPH) have identified a specific peptide that may block the entry of the hepatitis C virus (HCV) into the liver, representing ...

Researchers suggest approach to fight common virus in immunosuppressed patients

August 20, 2015
Using an animal model they developed, Saint Louis University and Utah State university researchers have identified a strategy that could keep a common group of viruses called adenoviruses from replicating and causing sickness ...

Timing, duration of biochemical bugle call critical for fighting viruses

June 13, 2012
Researchers have identified the primary player of the biochemical bugle call that musters the body's defenders against viral infection.

Recommended for you

HIV exports viral protein in cellular packages

February 15, 2018
HIV may be able to affect cells it can't directly infect by packaging a key protein within the host's cellular mail and sending it out into the body, according to a new study out of a University of North Carolina Lineberger ...

Can gene therapy be harnessed to fight the AIDS virus?

February 13, 2018
For more than a decade, the strongest AIDS drugs could not fully control Matt Chappell's HIV infection. Now his body controls it by itself, and researchers are trying to perfect the gene editing that made this possible.

Big data methods applied to the fitness landscape of the HIV envelope protein

February 7, 2018
Despite significant advances in medicine, there is still no effective vaccine for the human immunodeficiency virus (HIV), although recent hope has emerged through the discovery of antibodies capable of neutralizing diverse ...

Scientists report big improvements in HIV vaccine production

February 5, 2018
Research on HIV over the past decade has led to many promising ideas for vaccines to prevent infection by the AIDS virus, but very few candidate vaccines have been tested in clinical trials. One reason for this is the technical ...

Microbiome research refines HIV risk for women

January 25, 2018
Drawing from data collected for years by AIDS researchers in six African nations, scientists have pinpointed seven bacterial species whose presence in high concentrations may significantly increase the risk of HIV infection ...

Researchers find latent HIV reservoirs inherently resistant to elimination by CD8+ T-cells

January 22, 2018
The latest "kick-and-kill" research to eliminate the HIV virus uncovered a potential obstacle in finding a cure. A recent study by researchers at the George Washington University (GW) found that latent HIV reservoirs show ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.