RNA-Interference Technology Unveils Potential New Targets For HIV Drugs

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Thermo Fisher Scientific's RNA-interference (RNAi) technology has enabled a groundbreaking study at Harvard Medical School in Boston, which identified human proteins required for growth of the human immunodeficiency virus (HIV). This research points to potential new targets for treating HIV infection, which causes acquired immune deficiency syndrome (AIDS).

In the study, Harvard Medical School researchers used the Thermo Scientific Dharmacon siGENOME siRNA Library to "silence" more than 21,000 human genes, blocking the proteins they produce. With the help of Harvard's ICCB-Longwood High Throughput Screening Facility, the researchers identified 273 proteins required for HIV reproduction. Only 36 were previously known to be important to HIV.

"This study clearly demonstrates the power of genome-wide RNAi screening in identifying novel drug targets," said Ian Jardine, vice president of global research and development for Thermo Fisher Scientific. "The Harvard Medical School findings dramatically expand the number of potential targets for fighting HIV. It is an exciting discovery that holds promise for new treatments, and we are thrilled that our genome-wide siRNA library enabled this work."

Current HIV therapies target the virus itself, but HIV often mutates to build resistance against those drugs. Drugs targeting host proteins may be significantly less vulnerable to resistance caused by the virus' ability to mutate.

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The research team was led by Harvard Medical School (HMS) professor Dr. Stephen J. Elledge and Dr. Judy Lieberman, HMS professor of pediatrics as well as an investigator at the Immune Disease Institute and director of the HMS Division of AIDS. The team also included Dr. Abraham L. Brass, postdoctoral researcher, working with Derek Dykxhoorn and Nan Yan, molecular virologists in Dr. Lieberman's group. Brass used the Dharmacon siGENOME siRNA Library for discovering weaknesses in pathogens such as HIV.

"HIV only expresses a few proteins, so it depends greatly on our cellular machinery during its lifecycle," said Brass. "Every time the virus relies on one of our proteins, it gives us the potential to disrupt that interaction and hurt HIV, which is very exciting. We also now have the ability to combine technology like siRNA screening with advanced robotics, giving us an incredibly powerful tool to go after devastating diseases such as HIV and cancer."

Dr. Caroline Shamu, director of the ICCB-Longwood Screening Facility, added, "Whole-genome siRNA (short-interfering RNA) screening is playing an increasingly important role in advancing genomic and proteomic research. Because it allows us to investigate the entire human genome, screening thousands of samples simultaneously, it dramatically accelerates the pace of biomedical discovery." Shamu's facility hosts the Dharmacon siGENOME siRNA Library and oversees screening conducted by researchers from Harvard Medical School and its affiliates.

The siGENOME siRNA Library is a collection of more than 21,000 siRNAs targeting every gene in the human genome. Each siRNA silences or disrupts the gene's ability to produce a specific protein. The siGENOME siRNA Library is currently used by many of the world's leading research institutions to accelerate the identification of genes important to human health.

Harvard Medical School is a member of the RNAi Global Initiative, founded by the Dharmacon products team and several leading research institutions around the world. In addition to Thermo Fisher Scientific, there are now 26 member institutions, all using the siGENOME siRNA Library and collaborating on research into cancer, diabetes, infectious diseases and other human health problems.

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