By Nancy Parrish, Staff Writer
Earlier this year, the Office of AIDS Research (OAR) awarded two, two-year grants of $200,000 each to Anu Puri, Ph.D., and Robert Blumenthal, Ph.D., both of the Center for Cancer Research (CCR) Nanobiology Program, and to Eric Freed, Ph.D., of the HIV Drug Resistance Program, for their research on potential new treatments for HIV.
In its announcement, OAR indicated that the grants were awarded in support of the U.S.–India Joint Working Group (JWG) on the Prevention of Sexually Transmitted Diseases and HIV/AIDS. The proposals submitted by Puri and Freed underwent a two-level peer review process that involved scientists from both the National Institutes of Health and the Indian Council of Medical Research, the lead agencies under JWG. “These projects will further develop crucial research infrastructure and capacity building between U.S. and Indian biomedical research communities,” the announcement letter stated.
Puri to Develop Nano-Drug Delivery System
Lead investigator Puri said her group is using their grant to develop a drug delivery system that uses targeted nanoparticles containing FDA-approved anti-HIV-1 drugs. Currently available drugs are aimed at interrupting the virus’s life cycle and are primarily designed to be delivered systemically, Puri explained. However, these drugs “are limited by common elements such as poor bioavailability, systemic toxicity, and development of drug resistance.” In addition, these drugs can cost as much as $25,000 per year, she said.
“Nano-drug delivery systems, coupled with site-specific targeting ligands, constitute a promising system to boost efficacy and bioavailability of existing drugs and pharmaceuticals,” Puri said. “Our objective is to increase the efficacy, reduce toxicity, bypass multidrug resistance and make the treatments affordable in countries such as India.”
Puri and Blumenthal will work with investigators from the CCR Cancer and Inflammation Program, Dimiter Dimitrov, Ph.D., and Weizao Chen, Ph.D., as well as with Sanjay Malhotra, Ph.D., head, Laboratory of Synthetic Chemistry, SAIC-Frederick. As an expert in the area of protein engineering, Dimitrov will design HIV-1 specific ligands, Puri said, and Chen will be “instrumental in generating suitable small protein ligands.” Malhotra will be involved in the “modification of existing drug molecules for successful incorporation into nanoparticles,” she added.
Puri is collaborating with Rinti Banerjee, Ph.D., professor, Department of Biosciences and Bioengineering, Indian Institute of Technology, Bombay. She anticipates travelling to India “to transfer the targeted nanoparticles technology and provide insights into lipid assemblies and the fundamentals of viral entry pathways.” She will also learn about the nanocochleates formulation technology that Banerjee is developing, she said. In addition, she will use the opportunity to “deliver educational seminars and provide guidance to the students there, especially in the area of HIV‐1/AIDS and nanodrug delivery technology.”
Freed’s Research to Focus on Virus Maturation
Freed plans to develop anti-HIV drugs known as maturation inhibitors. “These compounds block the maturation step in the virus replication cycle,” he said, which is “a process triggered by the cleavage of the viral structural protein Gag by the viral protease. The maturation step is essential for the virus to become infectious after it is released from the infected cell,” he said.
Freed will collaborate with Ritu Gaur, Ph.D., associate professor, Life Sciences and Biotechnology, South Asian University, New Delhi, India. Gaur, who was a postdoc in Freed’s laboratory about 10 years ago, is now a principal investigator in her own laboratory, Freed said. They plan to “test the efficacy of these compounds against viral isolates prevalent in the U.S. and Europe (so-called subtype B) as well as subtype C strains prevalent in India,” Freed said.
As HIV becomes increasingly resistant to currently available drugs, new drugs are becoming necessary, Freed noted. He hopes that the research made possible by the grant will help increase the understanding of HIV assembly and maturation, which in turn will advance the development of novel inhibitors toward clinical use. “It is our hope that the novel maturation inhibitors that we are currently developing and testing will prove effective not only against strains of HIV-1 circulating in the U.S. and Europe, but also against those prevalent in developing regions of the world,” including Africa and India.
Eric Freed, Ph.D., right, is working with Ritu Gaur, Ph.D., South Asian University, New Delhi, India, to develop anti-HIV drugs known as maturation inhibitors. At left is Gaur, who spent a month working in Freed’s lab earlier in the summer.