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 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.
Lentiviral delivery vectors must be engineered to target only specific cell type, as seen in A of the diagram. Once the engineered virus encounters HIV, it would inject itself and neutralize the virus. These neutralizing antibodies (B) would immunize the body against HIV over a person’s lifetime.