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Old 08-31-2010, 11:43 AM   #1
Rich66
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RNAi therapy

RNAi and cancer: Implications and applications (2006)
FREE TEXT

ABSTRACT
RNA interference (RNAi) is an endogenous process that regulates expression of genes and corresponding proteins to maintain homeostasis in diverse organisms. Non-coding RNAs (ncRNAs) including both long and short ncRNAs are widely expressed and levels of some specific microRNAs are different in tumor and
non-tumor tissues. RNAi has been invaluable for unraveling critical pathways involved in cancer development, growth and metastasis and has identified critical tumor-type specific gene targets for chemotherapy. In addition, the development of new derivatized small inhibitory RNAs and more efficient methods of their delivery
will facilitate the future development of these ribonucleotides as cancer chemotherapeutic agents.




http://phx.corporate-ir.net/phoenix....620&highlight=

Quote:
About RNA Interference (RNAi)
RNAi (RNA interference) is a revolution in biology, representing a breakthrough in understanding how genes are turned on and off in cells, and a completely new approach to drug discovery and development. Its discovery has been heralded as "a major scientific breakthrough that happens once every decade or so," and represents one of the most promising and rapidly advancing frontiers in biology and drug discovery today which was awarded the 2006 Nobel Prize for Physiology or Medicine. RNAi is a natural process of gene silencing that occurs in organisms ranging from plants to mammals. By harnessing the natural biological process of RNAi occurring in our cells, the creation of a major new class of medicines, known as RNAi therapeutics, is on the horizon. Small interfering RNAs (siRNAs), the molecules that mediate RNAi and comprise Alnylam's RNAi therapeutic platform, target the cause of diseases by potently silencing specific mRNAs, thereby preventing disease-causing proteins from being made. RNAi therapeutics have the potential to treat disease and help patients in a fundamentally new way.
A Protein Killer Could Treat All Cancers, and Possibly All Illnesses

By Corey Binns Posted 08.23.2010

Quote:
The biotech company Alnylam announced in June that its drug ALN-VSP cut off blood flow to 62 percent of liver-cancer tumors in those 19 patients, by triggering a rarely used defense mechanism in the body to silence cancerous genes. Whereas conventional drugs stop disease-causing proteins, ALN-VSP uses RNA interference (RNAi) therapy to stop cells from making proteins in the first place, a tactic that could work for just about any disease. “Imagine that your kitchen floods,” says biochemist and Alnylam CEO John Maraganore. “Today’s medicines mop it up. RNAi technology turns off the faucet.”
Quote:
The technique’s ability to attack single genes could lead to drugs for the 75 percent of cancer genes that lack any specific treatment, as well as for other illnesses. Alnylam is already testing RNAi therapy for Huntington’s disease and high cholesterol in cell cultures; other researchers are tackling macular degeneration, muscular dystrophy and HIV. The potential has driven nearly every major pharmaceutical company to start an RNAi program. Because the approach is fundamentally simple, RNAi therapy could be ready within two years, say experts including John Rossi, a molecular geneticist at City of Hope National Medical Center in California. Alnylam plans to enroll an additional 36 patients in the ALN-VSP trial and increase the dosage, but the early results are good enough to suggest that it could be among the first RNAi therapies to hit the market. “I think RNAi could work for anything,” Rossi says. “But even if it only works for liver cancer, it would be pretty good.” For liver-cancer patients who have been failed by chemotherapy and radiation and felt their harsh side effects, that would be wonder drug enough.


http://www.biotechpharmanews.com/new...-and-csn5.html

Tekmira Expands Oncology Pipeline With RNAi Therapeutic Targeting Novel Cancer Genes WEE1 and CSN5



hursday, 02 June 2011 07:11 Tekmira Pharmaceuticals Corporation (Nasdaq:TKMR) (TSX:TKM), a leading developer of RNA interference (RNAi) therapeutics, announced today that it has secured licenses from Alnylam Pharmaceuticals, Inc. under its InterfeRx™ program to develop a new RNAi therapeutic targeting two validated oncology targets: WEE1 and CSN5.
"Our collaborators at the National Cancer Institute (NCI) have identified the novel cancer genes WEE1 and CSN5 from human tumor samples, and together we have generated encouraging preclinical data by leveraging our expertise in siRNA design and delivery. We are excited about the opportunity to develop an RNAi therapeutic targeting these two unique cancer genes," said Dr. Mark J. Murray, Tekmira's President and CEO.
Some highlights from the promising data generated in collaboration with Tekmira's partners at the National Cancer Institute and published in leading scientific journals and at scientific conferences include:
  • Gene expression data from human tumor samples indicate that both CSN5 and WEE1 are up-regulated in a number of human cancers and have been identified as potential molecular targets in breast, liver, lung, ovarian and skin cancer, amongst other tumor types. These key genes promote tumor cell growth and cancer pathogenesis.
  • WEE1 is a tyrosine kinase that regulates cell cycle progression and the response to DNA damage by its control of a cell cycle checkpoint that precedes entry into cell division. Inhibiting WEE1 increases cancer cell sensitivity to DNA damaging agents and other therapies.
  • CSN5 is the catalytic center of the COP9 signalosome, a multi-protein complex involved in regulating protein degradation via the ubiquitin proteasome pathway. CSN5 regulates protein turnover and other protein interactions that affect many stages of tumorigenesis. Silencing of CSN5 causes molecular changes that inhibit tumor cell growth and increases apoptosis (programmed cell death).
  • Lipid nanoparticle (LNP) delivery of siRNA targeting WEE1 effectively suppresses tumor growth and increases the survival of treated animals in preclinical models of human hepatocellular carcinoma (HCC or liver cancer) in a dose-dependent manner.
  • LNP delivery of siRNA against CSN5 resulted in 80% inhibition of tumor cell growth in vitro and significant reduction in tumor growth in preclinical models of human liver cancer.
  • A combination RNAi approach that depletes both WEE1 and CSN5 may be ideal for inactivating multiple pathways that promote cancer, and to avoid cellular resistance. Combinations of WEE1 and CSN5 siRNA resulted in a significant increase in apoptosis in human liver cancer cells in vitro, relative to the action of each siRNA alone.
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Old 08-31-2010, 11:44 AM   #2
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Old 08-31-2010, 12:00 PM   #3
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