A Fred Hutch and University of Washington team of virologists and bioengineers led by Dr. Keith Jerome has received a $200,000 grant — the first phase of up to $1.5 million in milestone-driven funding over four years — to develop nanocarrier technology to deliver therapies to reservoirs of dormant, HIV-infected cells.
The grant is from the New York-based amfAR, or Foundation for AIDS Research, as part of its "Countdown to a Cure for AIDS" initiative, which aims to achieve the scientific underpinnings of a cure by 2020. The hard-to-reach reservoirs are a key barrier to curing HIV.
Almost immediately upon infection, HIV begins to integrate itself into the DNA of some of the longest-lived cells of the body. There the virus lies dormant, unaffected by the lifesaving antiretroviral drugs that keep actively replicating HIV in check. But stop the medication, and the reservoirs rekindle infection.
Nanocarriers are extremely small particles that can be bioengineered to carry drugs to specific cells while limiting toxicity to other cells. In this case, the nanocarriers will target latently HIV-infected CD4 T cells in fluids and lymphoid tissues. Some of the nanocarriers will deliver latency- reversing agents in keeping with an HIV-cure approach that seeks to “kick,” or reawaken, the dormant virus so that it can then be killed.
What’s most unique about the study underway, said Jerome, is that other nanocarriers will deliver an antiproliferative agent called MMF. The project will test a hypothesis by Fred Hutch’s Dr. Joshua Schiffer, a mathematical modeler in the Vaccine and Infectious Disease Division, and Dr. Florian Hladik, an HIV expert also in VIDD, that slowing the replication rate of latently infected CD4 T cells will decrease the reservoir more rapidly than latency reversal alone.
“[Schiffer’s] mathematical models suggest that if one can slow down the rate of proliferation, one might dramatically speed the decay of the HIV reservoir,” Jerome said. “We have this particle that can get the antiproliferates to the right place and we can test this hypothesis to see if we get a measurable acceleration in decay of the reservoir.”
Schiffer is a co-investigator of the study, as is Hladik of Fred Hutch and UW. Another co-investigator, the UW’s Dr. Kim Woodrow, is a bioengineer who developed the nanoparticles and was critical to designing the proposal. Also on the project are UW microbiologists Drs. Shiu-Lok Hu and Robert Coombs, Fred Hutch statistician Dr. Amalia Magaret and Pharmacokinetics Lab Director Dr. Jeannine McCune, and University of Louisiana-Lafayette pathologist Dr. Francois Villinger.
Jerome is head of UW Virology, director of its Molecular Virology Laboratory and co-director, with Dr. Hans-Peter Kiem, of the Fred Hutch-based defeatHIV research group, which is studying cell and gene therapy and immunotherapy approaches to curing HIV.
Mary Engel is a former staff writer at Fred Hutchinson Cancer Center. Previously, she covered medicine and health policy for the Los Angeles Times, where she was part of a team that won a Pulitzer Prize for Public Service. She was also a fellow at the Knight Science Journalism Program at MIT. Follow her on Twitter @Engel140.