NEW YORK, Jan. 25, 2016 --- In a move that adds extraordinary new dimensions to the field of HIV cure research, amfAR, The Foundation for AIDS Research, has recruited the expertise of a world-renowned physicist and a leading polymer chemist. The Foundation has awarded $1 million each over four years to Harvard physicist Dr. David Weitz and bioengineer and polymer scientist Dr. Alexander Zelikin of Aarhus University in Denmark. The two will bring their expertise to bear in the effort to eradicate the viral reservoir that is considered the principal barrier to curing HIV.
The new awards are the latest to be funded by amfAR through its $100 million Countdown to a Cure for AIDS initiative, whose goal is to develop the scientific basis for a cure by 2020. The grants were aimed specifically at recruiting the expertise of scientists working outside the field of HIV in areas that could directly inform efforts to cure HIV. Drs. Weitz and Zelikin will collaborate with leading AIDS researchers Dr. Bruce Walker at Harvard and Dr. Martin Tolstrup at Aarhus University, respectively.
“Research to find a cure for AIDS has evolved from a process of discovery to a challenge of technology,” said amfAR Chief Executive Officer Kevin Robert Frost. “And recent technological advances have brought with them some exciting opportunities for the cross-pollination of ideas and for adapting cutting-edge technologies to the field of HIV cure research.”
Dr. Weitz, who is the Mallinckrodt Professor of Physics and Applied Physics at the John A. Paulson School of Engineering and Applied Sciences at Harvard University, is a world leader in the field of microfluidics. This cutting-edge scientific field, which involves the manipulation of minuscule volumes of fluid using state-of-the art devices and processes, has already revolutionized a wide array of scientific fields.
Dr. Weitz has developed a technique that uses fluid mechanics to specifically isolate the most effective killer T cells from those that are less potent. He proposes to isolate these cells—a critical weapon of the immune system against virally infected cells—from patient samples, clone them in a petri dish, and use a mouse model to test whether the reinjection of these killer cells can lead to a functional cure of HIV.
Dr. Zelikin is an expert in prodrugs—temporarily inactive drugs that become active only when instructed by a second stimulus—which he plans to use to eliminate the HIV reservoir. The project will design a two-component cocktail. One prodrug will be developed to gently reawaken the latent HIV using a drug that Dr. Martin Tolstrup, a virologist and HIV expert, has shown to be effective in patients. The second prodrug will be designed to specifically initiate the killing of virally infected cells. Acting in tandem, the two prodrugs administered together are poised to specifically activate the latent viral reservoir and kill the cells harboring HIV.
“The ‘outside the box’ approaches proposed by Drs. Weitz and Zelikin will both expand and invigorate the field of HIV cure research,” said Rowena Johnston, Ph.D., amfAR Vice President and director of research. “We are tremendously excited to be supporting these studies, each of which holds enormous potential for depleting, and perhaps even clearing, the persistent reservoir of HIV.”
Investment Grants 2016
PI: David Weitz, PhD
Collaborating HIV Scientist: Bruce Walker, MD
Eradicating the HIV reservoir: Using microfluidics to exploit killer T cells
Killer T cells are part of the immune system’s arsenal against virally infected cells. Despite their name, not all members of this group are equally effective in killing HIV-infected cells. To date, efforts to isolate killer T cells with the most potent killing potential have been too broad to deliver the results needed to make strides against disease. This problem is being solved by Dr. David Weitz, a physicist and world recognized leader in microfluidics. Dr. Weitz has harnessed his years of cutting-edge contributions of applied physics in biology, by developing a machine that uses fluid mechanics to specifically isolate the best, most effective killer T cells from those that are less potent. He proposes to isolate these killers from patient samples, clone them in a petri dish, and use a humanized mouse model to test whether the reinjection of these killer cells can lead to a functional cure of HIV. His collaboration with Dr. Bruce Walker, an HIV pioneer whose studies have defined the field of HIV immunology, will ensure that this novel, microfluidic-based approach will test the necessary elements that could lead to T cell therapy in humans.
PI: Alexander Zelikin, PhD
Collaborating HIV Scientist: Martin Tolstrup, PhD
Aarhus University, Aarhus, Denmark
Tandem latency reversal and suicide prodrugs to eliminate HIV reservoirs
A major obstacle to HIV eradication is the presence of a latent viral reservoir that is established soon after infection. This cryptic reservoir, responsible for the viral rebound once the patient is off antiretroviral therapy, is difficult to locate and the body’s immune system is unable to clear the viral reservoir. An approach to circumvent these issues is offered here by a bioengineer and polymer chemist, Dr. Alexander Zelikin. The project builds on Dr. Zelikin’s expertise in developing prodrugs—labile drugs that become active when instructed by a specific stimulus. The project will design a two-component cocktail. One prodrug will be developed to gently reawaken the latent HIV using a drug that Dr. Martin Tolstrup, a virologist and HIV expert, has shown to be effective in patients. The second prodrug will be designed to specifically initiate the killing of virally infected cells. Acting in tandem, the two prodrugs administered together are poised to activate the latent viral reservoir and kill the cells harboring HIV.
amfAR, The Foundation for AIDS Research, is one of the world’s leading nonprofit organizations dedicated to the support of AIDS research, HIV prevention, treatment education, and the advocacy of sound AIDS-related public policy. Since 1985, amfAR has invested $450 million in its programs and has awarded grants to more than 3,300 research teams worldwide. Learn more about amfAR at www.amfar.org.
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