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Alnylam Pharmaceuticals, Inc. Message Board

  • pasadenaphd pasadenaphd Apr 7, 2006 5:24 PM Flag

    Novartis Publication

    IDrugs. 2006 Apr;9(4):279-82.

    Using RNAi in the clinic.

    Dev KK.

    Novartis Institutes for BioMedical Research, Neuroscience Research, Novartis Pharma AG, WSJ 386-7-43, CH-4002 Basel, Switzerland.

    RNA interference (RNAi) is a biological process that controls gene silencing in all living cells. Targeting the RNAi system represents a novel therapeutic strategy that has the ability to intercede with multiple disease-related genes and so target many human diseases. Recently, the design of small interfering RNA (siRNA)-selective compounds has become more straightforward because of the significant progress made in predictive modeling. Exciting new data show that siRNA blocks gene function in vivo, suggesting that it has potential as a therapeutic approach for humans. This article highlights recent advances in siRNA research and discusses the aims of the pharmaceutical and biotechnology industries to progress siRNA compounds into the clinical. In the fight against disease, the use of RNAi is a powerful new tactic that adds to the arsenal of small-molecule inhibitors and antibody-blocking approaches.

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    • What people should get from this is:

      the use of RNAi is a powerful new tactic that adds to the arsenal of small-molecule inhibitors and antibody-blocking approaches.

      Does anyone here see RNAi as being FAR FAR more useful and effective than the current batch of antibody drugs doing the rounds that are pumping DNA, AMGN and the like higher and higher.

      A good example would be the lastest PFE purchase. I know a few people who work at Rinat....great scientists to be sure....but what do they anti-NGF antibody. Is this what PFE just paid a few 100 M for....its insane. PFE, are you hearing me, buy BLT for god sakes. 15M AUD is chump change for you. Ok, so you will have to pay a lot more to get full ownership...please do, make me rich in the process and do yourself a favor.

      Next, Herceptin. This is a great drug for Roche and patients alike...but this antibody approach (think unstable lyophilized antibody which you must add sterile buffer to before starting your once weekly 90 min infusion) really in the same ballpark as RNAi will be.

      Why not just turn off the goddam EGFR with RNAi. I am sure future generations of RNAi will be far more stable than Humanized antibodies like Herceptin (please store at 4C or else it won't work) and more effective and specific too with lower side-effects. If it is possible to goddam infuse an antibody (that causes severe immune responses in some people) then I am sure RNAi will be just fine to use.

      People, we are truly on the verge of something extraordinary.

      • 3 Replies to pfizerbull
      • You are wrong about antibody treatments. In the history of cancer therapeutics nothing has been more specific, effective, and non-toxic. Moreover, siRNA may not be particularly effective against cancer because so many genes are involved. Even when cancer cells are treated in culture with siRNAs targeting Kras mutations or EGFR they don't die. Usually they go into growth arrest which makes them resistant to other types of chemotherapy. There are no magic bullets when it comes to cancer, and anyone who tells you that there is, is selling something.

      • Good summary. I survey all of the RNAi literature and attend scientific conferences where I discuss the miRNA/SiRNA results with the researchers.IMO, this really is a revolutionary technology.Researchers are not concerned about interferon response anymore, less concerned about non-specific effects, and solving delivery by various means.Having myself managed HT R&D to find new actives (prior to discovery of RNAi), the sheer potency (nM) of RNAi impresses me, and can help on specificity issue.

      • >Why not just turn off the goddam EGFR with RNAi...<

        This is certainly a possibility because cancer cells have a unique EGFR--it is mutated and activated without external signal. In case of EGFR1 the mutation occurs in the ATP binding pocket of its kinase portion. In theory siRNA against this region can be made. However, mutation is highly heterogeneous... differs from tumor to tumor and possibly a late stage differs from an early stage. So, specificity and activity will be lost. If one were to use different parts of EGFR molecule which is not mutated, then siRNA against such portion would also act against EGFR in normal cells such as skin cells. This is my thought... I am not a trained molecular biologist. I invite other true molecular oncologists to contribute to your interesting idea.

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