Therapeutics/Drugs

Marilyn Fernandez of Altor Bioscience Corporation in the U.S. will engineer single chain T cell receptors (TCR) to deliver immunotherapies to HIV-infected cells. These TCRs will be engineered to recognize known viral variants to linked to the emergence of drug-resistant HIV mutations.

Anne Moscona of Weill-Cornell Medical College will investigate a new approach to treating respiratory viral disease by using artificial cell-like structures to present molecules that would attract the virus and activate the fusion mechanism it uses to enter cells. By triggering this mechanism prematurely, viruses can't enter target cells and cause infection.

Tayyaba Hasan of Harvard University in the U.S. will work to design a conjugate which will attach to the GP63 enzyme of the Leishmania parasite. This therapy will consist of a lightactivatable, non-toxic chemical that will be activated by a light source, killing the parasite but leaving surrounding cells intact.

Dan Feldheim of the University of Colorado in the U.S. will test his hypothesis that gold nanocrystals coated with drug compounds can effectively inhibit protein- protein interactions that often drive disease pathogenesis, will be less susceptible to evolutionary mechanisms that lead to drug resistance, and offer enhanced drug delivery characteristics. This project's Phase I research demonstrated that gold nanocrystals can be tailored to circumvent many viral and bacterial evolutionary drug resistance mechanisms.

Manipulation of skin cells can now create pluripotent cells which can proliferate and differentiate into many human cell types. This new technology will be employed by Jeanne Loring of the Burnham Institute for Medical Research to generate pluripotent cell lines for ethnically diverse populations to be used a genetically appropriate model to develop more specific and appropriate therapies against infectious disease.

Roy Kishony of Harvard University will seek to identify chemical entities that act as "selection inverters" which actively target antibiotic-resistant bacteria. Selection- inverters could be used in combination with traditional antibiotics to prevent resistance and possibly even drive a drug-resistant bacteria population back to drug sensitivity.

George O'Toole, a microbiologist at Darmouth Medical School, and Mark Grinstaff, a biomedical engineer and chemist at Boston University, will work to develop an expansile nanoparticle, packed with high concentrations of antibiotics, which would expand and release their content when internalized by host cells. The hope is that more precise delivery of high concentrations of antimicrobial agents, in single or combination therapies, will reduce the development of resistance.

A3G, protein found in human cells that inactivates several viruses including HIV, is "switched off" in proliferating T cells. Harold Smith of the University of Rochester will screen for small molecule compounds that bind to A3G in cells and turn its anti-viral activity back on.

Ron Raines of the University of Wisconsin proposes to convert a ribonuclease that rapidly degrades RNA into a zymogen, an enzyme precursor that is activated only when cleaved by an HIV protease. Because this cleaving can only occur within HIV-infected cells, the toxic activity of the ribonuclease will be unleashed only in cells in which HIV is active.

Employing new high throughput methods, antibiotic screening technologies and rapid genomic sequencing methods, George Church of Harvard University will partner with labs in South Africa to develop a new approach to identifying, studying, and limiting emerging drug resistance.