Scientists have developed a method that uses antibodies to deliver the RNA directly into immune cells in a study that shows that short strands of RNA could help to dramatically suppress HIV infection in mice.
Using RNA interference (RNAi)methods that target particular viral genes has seemed like a promising, less toxic alternative. But research has been hampered by the limitations of the small-animal models of HIV infection.
Now, proof-of-concept studies, using newer mouse models have shown that it is possible to use short interfering RNAs (siRNAs)to combat HIV.
Priti Kumar of Harvard Medical School, Boston, and her colleagues used mice lacking their own immune systems and into which researchers had introduced human haematopoietic stem cells, which give rise to all the different types of blood cell, to reconstitute an immune system closely resembling our own.
The research, published this week in Cell1 and reported by Nature used antibodies to target the siRNAs specifically into one of the key types of immune cell that is a target of HIV. In some cases, this treatment dramatically cut viral infection.
The antibodies used in the study bind to CD7 proteins on the surfaces of T cells, a type of white blood cell that plays a key role in immunity and which is one of the main cell types that HIV infects. The researchers attached the anti-HIV siRNAs to these antibodies, which delivered the strands exclusively to T cells.
Three different siRNAs were used. One stops the cell producing the surface receptor protein that HIV uses to enter the T cell; the other two siRNAs target HIV’s own genes, preventing the virus from replicating if it does manage to get into the cell.
"Overall, I see this work as an exciting proof of principle," John Rossi of the Beckman Research Institute of the City of Hope, Duarte, California, who has worked extensively on RNAi therapies, said. "This is a strategy that can be developed for clinical applications in humans," Kumar said.
"This approach is likely to help in bringing down the viral load in patients that don’t respond to standard highly active antiretroviral therapy (HAART)," Ramesh Akkina of Colorado State University, Fort Collins, who also works on siRNA delivery, said. But he notes that such a therapy could become ineffective if the antibody-siRNA combination provokes an unwanted response by the immune system.