Therapeutics/Drugs

Johnny He of Indiana University proposes to engineer biodegradable nanoparticles that target active and latent HIV-infected cells by binding to the carbohydrate portion of the protein gp120, which the virus uses to seek out host cells. The "sticky" nanoparticles would then bind HIV, either in the blood, or within cells, killing the virus.

HIV has a very high rate of mutation allowing it to very rapidly develop resistance to AIDS therapies. The essential viral enzyme, HIV reverse transcriptase, lacks a "proofreading" or "repair activity" leading to errors or mutations. Karen Anderson of Yale University is working on "stealth" compounds that have a unique anchor specific for HIV. These compounds encourage the virus to make mutations until the virus is annihilated.

Dan Kaufman of the University of Minnesota will test whether natural killer cells, generated from stem cells can effectively target and eliminate HIV-infected cells.

Abraham Pinter of the University of Medicine and Dentistry of New Jersey will study the mechanisms that make neutralizing epitopes within conserved sites of the HIV virus resistant to antibodies, and will screen for reagents that can "unmask" these epitopes so that antibodies can target and eliminate the virus.

While humans and chimpanzees share an overwhelming similarity between genes, primates exhibit a resistance to AIDS. Walter Messier of biotechnology company Evolutionary Genomics in the U.S. will research the mechanisms of eight genes that have adapted in chimps to identify how viral suppression works.

Keith Jerome of the University of Washington in the U.S. will utilize a class of proteins called homing endonucleases, which have the ability to cut DNA sequences, to target the DNA sequences unique to HIV, thus disabling the virus from making any more copies of itself. This project's Phase I research demonstrated that homing endonucleases can find a model virus hidden in the genes of infected cells. In Phase II, Jerome's team is now modifying these proteins in hopes of producing several that can specifically target and destroy HIV within infected cells.

HIV uses protein interaction pathways to force host cells to make more HIV copies. Judith Klein of Carnegie Mellon University aims to use advanced computational methods to predict parallel pathways that can be found and used to circumvent the points of HIV interception.

Olaf Kutsch of the University of Alabama proposes that HIV latency is controlled by host-gene promoter interference, a mechanism that prevents the initiation of viral gene expression. Understanding how host-gene promoter interference controls latent HIV-1 infection may aid development of therapies to deplete latent HIV in patients.

Douglas Watson and colleagues of SRI International will engineer probiotic bacteria that produce Vitamin A to test the hypothesis that these bacteria will stimulate healthy immunity in the GI tract and reduce the impact of diarrheal diseases.

The intestinal disease cholera uses cell-to-cell signaling to coordinate its growth and virulence in the human gut. John March of Cornell University in the U.S. is developing strains of commensal bacteria that naturally reside in the gut to express the key chemical signals used by cholera to abort the colonization process and allow the pathogen to pass through the G.I. system without causing symptoms.