"Smart Bomb" RNA Molecule Could Take Out Drug-Resistant HIV
Researchers have engineered an RNA molecule to block freely circulating HIV as well as replication inside infected cells. Tests in mice engineered to be susceptible to HIV showed the chimeric RNAs reduced HIV-1 replication by several orders and staved off viral-induced CD4+ T-cell declines, say researchers.
One part of the RNA molecule has a high binding affinity to the gp120 protein found on the surface of HIV's envelope and on HIV-infected cells. It is designed to neutralize free-floating HIV in the blood and attach to and deliver into infected cells a small interfering RNA (siRNA) "that triggers sequence-specific degradation of HIV RNAs," the study authors wrote.
"You're only targeting what has to be targeted," said co-author John Rossi, a molecular biologist at the City of Hope's Beckman Research Institute in Duarte, Calif., who likened the molecule to a "smart bomb."
The molecule could someday figure into combination or stand-alone therapy, Rossi said. The antiviral effect of the chimera lasts about a week, so any treatment would require regular injections.
"They do see quite dramatic inhibition" of HIV, said Ben Berkhout, a retrovirologist at the University of Amsterdam. But most seems traceable to the anti-gp120 aptamer, or binding affinity, rather than the work of the siRNA, he said. "I haven't seen the double action of this combination," he said.
Rossi and colleagues found that in comparison to the aptamer alone, its combination with siRNA provided more extensive inhibition. The team found siRNA in the lymphocytes of treated mice, and measurements of the two targeted sequences -- tat and rev -- in such cells were 75 percent to 90 percent lower after treatment. Tat and rev genes also were cut in the right spots, indicating the molecule worked.
The study, "An Aptamer-siRNA Chimera Suppresses HIV-1 Viral Load and Protects From Helper CD4+ T Cell Decline in Humanized Mice," was published in Science Translational Medicine (2011;3(66):p66ra6).