Therapeutics/Drugs

Terri Finkel of The Children's Hospital of Philadelphia in the U.S. will test whether synthetic BET (bromodomains and extraterminal) protein antagonists can inhibit the replication of HIV and the establishment of latency, while also promoting the reactivation of latently infected cells. Such molecules could be used to control and cure HIV infection.

Phillip M. Gerk of Virginia Commonwealth University in the U.S. will test the ability of fatty acid transporters to deliver antiretroviral drugs to the central nervous system and gut-associated lymphatic tissues, which provide sanctuary for latent HIV.

Thor Wagner of Seattle Children's Hospital in the U.S. will use high-throughput single-cell screening of activated B-cells from HIV patients on antiretroviral therapy in an effort to identify antibodies that bind specifically to HIV-infected cells. These antibodies could be used to develop antibody drug conjugates to kill HIV-infected cells.

Adrienne Wilk of the University of Illinois at Chicago in the U.S. will investigate whether post-translational modification of S-acylated cell surface proteins alters the plasma membrane of cells with latent HIV infection. If so, these S-acylated proteins could be used to identify such latently infected cells that cannot be detected using current diagnostic methods.

Marco Sgarbanti at the Istituto Superiore di Sanità in Italy proposes to develop a new class of small molecules designed to mimic Tat gene products found in HIV that stimulate and accelerate the transcription of HIV RNA. These Tat-mimicking compounds could activate the latent virus, creating an opportunity to expose it to effective antiretroviral therapies.

Russell Poulter of the University of Otago in New Zealand will test 'homing' endonucleases found in the genomes of some microbes for their ability to precisely cleave DNA at very specific sites. If successful, these nucleases could be suitable for cleaving and eliminating integrated HIV.

Hongxiang Chen of Union Hospital, Tongji Medical College, Huazhong University in China will develop X-ray-sensitive fluorescent nanoparticles conjugated to antibodies that will selectively bind to HIV. Once bound to the targets, the nanoparticles can be excited by X-rays to kill the virus.

Marc-Andre Langlois of the University of Ottawa in Canada will develop small molecules that combine together to form a toxic compound only when they enter an HIV-infected cell. Because the molecules are non-toxic for healthy cells, they could constitute promising candidates for a vaccine-based delivery system aimed at specifically eliminating HIV-infected cells.

Nicolas Chomont of the Vaccine & Gene Therapy Institute Florida in the U.S. will determine if the stimulation of latently infected cells with HIV antigens is a viable strategy for eradicating the HIV reservoir. If successful, the strategy could be used to cure HIV by combining HAART and immunization with HIV antigens.

Fabio Romerio of the University of Maryland, Baltimore in the U.S. seeks to identify surface biomarkers of HIV latently infected cells by comparing membrane proteomes of latently infected and uninfected cells. Unique biomarkers allow selective killing of latently infected cells with specific ligands, or targeted delivery of chemotherapeutic agents.