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Manipulating the Smallest Building Blocks of Life to Defeat the World's Biggest Infectious Disease Killer

amfAR FUNDS CUTTING-EDGE GENE THERAPY APPROACHES TO HIV PREVENTION, TREATMENT, AND CURE

NEW YORK Feb 18, 2010 - amfAR, The Foundation for AIDS Research, on Thursday announced the recipients of its first ever awards for gene therapy research, supporting a broad range of strategies aimed at thwarting the virus both directly as well as by blocking its access to the cells it needs in order to replicate.

"This group of research projects constitutes a particularly strong first foray into this new and constantly evolving research field," said Rowena Johnston, Ph.D., amfAR's vice president and director of research. "amfAR is particularly pleased to play a role in supporting the creative thinking and bold efforts these scientists are bringing to the improved treatment and prevention of HIV, and possibly its cure."

The projects to be funded represent a broad range of gene therapy approaches to subverting the process of HIV infection and eradicating the virus. Dr. Keith Jerome of the University of Washington, for example, will be using homing endonucleases-a type of molecular scissors-to lethally cut up the HIV genome. Dr. Joseph Anderson of the University of California-Davis will explore a new and more efficient means of delivering gene therapy into the body of a patient, while Dr. Alejandro Balazs of the California Institute of Technology will use his amfAR funding to engineer and test a variety of immune interventions that could be developed into a vaccine. Dr. Balazs will conduct his research under the supervision of Nobel prize-winning scientist Dr. David Baltimore.

amfAR's interest in exploring the role of gene therapy in the eradication of HIV infection stems from a February 2009 report in the New England Journal of Medicine of a patient in Berlin with acute myeloid leukemia who underwent stem cell transplantation from an unrelated donor who carried a specific mutation that blocks HIV infection. To date, despite being off all antiretroviral therapy for more than two years, and off all immune suppressive medications, no HIV has been detected in this patient.
"For many years, gene therapy approaches to the treatment of disease have not lived up to their promise," said Dr. Johnston. "But the science has come a long way and there are good reasons to hope that this field of study could ultimately lead to the conquest of HIV."

More information about the 2010 amfAR gene therapy award recipients:

Lung-Ji Chang, Ph.D.
University of Florida, Gainesville, FL
$120,000
Combination of CCR5delta32 and siRNAs targeting HIV: Since effective gene therapy for HIV infection requires both the identification of the best target as well as an efficient means of delivering the gene therapy into cells, Dr. Chang plans to optimize both. In a test tube he will evaluate the ability of a lentiviral vector to deliver persistent gene therapy to cells. He will simultaneously test the ability of a variety of genetic manipulations to disrupt the function of the human CCR5 gene, known to be crucial to the ability of HIV to reproduce, as well as gene therapy targeted directly at the virus.

Keith Jerome, M.D., Ph.D.
University of Washington, Seattle, WA
$120,000
Engineering and characterization of HIV-specific homing endonucleases: Current antiretroviral therapy does not cure HIV infection because it destroys virus only when it is actively reproducing, leaving inactive viruses in their DNA form unscathed and able to reemerge to actively replicate at a later time. Dr. Jerome plans to test a method of targeting the genetic material of the virus directly via homing endonucleases, enzymes that could be designed to lethally cut the DNA of HIV. These enzymes could attack the virus regardless of whether it is reproducing, and may thus be a tool whereby HIV could eventually be eradicated.

Matthew Porteus, Ph.D.
University of Texas Southwestern Medical Center, Dallas, TX
$120,000
Using homologous recombination to stack genetic resistance to HIV infection: For over ten years scientists have known that individuals lacking a gene called CCR5 are almost entirely resistant to HIV infection. More recently, a drug that blocks CCR5 in infected people is effectively reducing virus levels. Recognizing the crucial role of CCR5, Dr. Porteus plans to genetically manipulate the CCR5 gene in cells in a test tube. He will use enzymes called zinc finger nucleases to lethally cut the DNA of the CCR5 gene, and will simultaneously insert the gene of a factor known to block HIV infection in monkeys. This way, he will use gene therapy to "stack" characteristics into cells that render them resistant to HIV infection.

Joseph Anderson, Ph.D./Mentor: Richard Pollard, M.D.
University of California-Davis, Sacramento, CA
$125,000

Direct injectable cell targeting vectors for improved HIV gene therapy: Gene therapy currently relies on modifying cells in a test tube and infusing them into the patient. Dr. Anderson plans to test a strategy for genetically modifying target cells within the body and thus overcome one of the hurdles of implementing gene therapy. He will engineer a lentiviral vector-or delivery system-to contain an antibody that will target it specifically to HIV-susceptible cells. The vector will carry inside it genes known to interfere with the ability of HIV to productively infect cells. Once this vector has been engineered, Dr. Anderson will test its ability to target the desired cells and render them resistant to HIV in a mouse model.

Alejandro Balazs, Ph.D./Mentor: David Baltimore, Ph.D.
California Institute of Technology, Pasadena, CA
$125,000
Creation of a synergistic immune response to HIV by gene therapy: There are two main types of immune response-humoral and cellular-that ultimately prevent or eliminate most infections, and they also contribute in varying proportions to the effectiveness of vaccines. One of the difficulties in developing an AIDS vaccine is an incomplete understanding of the characteristics of each of these immune responses that would most effectively combat HIV, and how to induce those responses in people. Dr. Balasz plans to use mice that have been engineered with human immune systems to test the relative contribution of humoral versus cellular immunity to the control of HIV infection.

Zhenya Ni, Ph.D./Mentor: Dan Kaufman, M.D., Ph.D.
University of Minnesota, Minneapolis, MN
$125,000
Engineer pluripotent stem cell derived NK cells to kill HIV infection: Several different cell types of the immune system exhibit a variety of anti-HIV effects. One of these cell types, natural killer (NK) cells, is effective against a wide variety of viruses including HIV. Dr. Ni plans to bolster the anti-HIV effects of NK cells by genetically engineering them with the characteristics of other powerful anti-HIV cells of the immune system, namely T cells. She will study the different mechanisms used by these genetically modified cells to kill HIV, and will test their ability to treat infection in a mouse that has been rendered susceptible to HIV.

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About amfAR

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 nearly $290 million in its programs and has awarded grants to more than 2,000 research teams worldwide.

 

Contact:

Cub Barrett, Program Communications Manager
(212) 806-1602

"Reproduced with permission - amfAR, The Foundation for AIDS Research"

amfAR, The Foundation for AIDS Research
www.amfar.org


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