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In the study, Harvard Medical School researchers used the ThermoScientific Dharmacon(R) siGENOME(R) siRNA Library to "silence" more than21,000 human genes, blocking the proteins they produce. With the help ofHarvard's ICCB-Longwood High Throughput Screening Facility, the researchersidentified 273 proteins required for HIV reproduction. Only 36 were previouslyknown to be important to HIV.
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"This study clearly demonstrates the power of genome-wide RNAi screeningin identifying novel drug targets," said Ian Jardine, vice president of globalresearch and development for Thermo Fisher Scientific. "The Harvard MedicalSchool findings dramatically expand the number of potential targets forfighting HIV. It is an exciting discovery that holds promise for newtreatments, and we are thrilled that our genome-wide siRNA library enabledthis work."
Current HIV therapies target the virus itself, but HIV often mutates tobuild resistance against those drugs. Drugs targeting host proteins may besignificantly less vulnerable to resistance caused by the virus' ability tomutate.
The research team was led by Harvard Medical School (HMS) professor Dr.Stephen J. Elledge and Dr. Judy Lieberman, HMS professor of pediatrics as wellas an investigator at the Immune Disease Institute and director of the HMSDivision of AIDS. The team also included Dr. Abraham L. Brass, postdoctoralresearcher, working with Derek Dykxhoorn and Nan Yan, molecular virologists inDr. Lieberman's group. Brass used the Dharmacon siGENOME siRNA Library fordiscovering weaknesses in pathogens such as HIV.
"HIV only expresses a few proteins, so it depends greatly on our cellularmachinery during its lifecycle," said Brass. "Every time the virus relies onone of our proteins, it gives us the potential to disrupt that interaction andhurt HIV, which is very exciting. We also now have the ability to combinetechnology like siRNA screening with advanced robotics, giving us anincredibly powerful tool to go after devastating diseases such as HIV andcancer."
Dr. Caroline Shamu, director of the ICCB-Longwood Screening Facility,added, "Whole-genome siRNA (short-interfering RNA) screening is playing anincreasingly important role in advancing genomic and proteomic research.Because it allows us to investigate the entire human genome, screeningthousands of samples simultaneously, it dramatically accelerates the pace ofbiomedical discovery." Shamu's facility hosts the Dharmacon siGENOME siRNALibrary and oversees screening conducted by researchers from Harvard MedicalSchool and its affiliates.
The siGENOME siRNA Library is a collection of more than 21,000 siRNAstargeting every gene in the human genome. Each siRNA silences or disrupts thegene's ability to produce a specific protein. The siGENOME siRNA Library iscurrently used by many of the world's leading research institutions toaccelerate the identification of genes important to human health.
Harvard Medical School is a member of the RNAi Global Initiative, foundedby the Dharmacon products team and several leading research institutionsaround the world. In addition to Thermo Fisher Scientific, there are now 26member institutions, all using the siGENOME siRNA Library and collaborating onresearch into cancer, diabetes, infectious diseases and other human healthproblems.
A paper written by the researchers details their findings and has beenpublished online by Science magazine. It will appea
