Future Treatment: siRNA

Penicillin WWII Advertisement. (Credit: Schenley Laboratories, Inc., Lawrenceburg, Indiana)

During 1940s, penicillin, the first commercially available antibiotic, was hailed as a “wonder drug.”  Penicillin helped make WWII the first American war where infection was not the major cause of death.  But by the 1950s, antibiotic resistance became widespread.  Scientists were engaged in a veritable arms race, constantly modifying and developing new classes of antibiotics to beat resistance while bacteria, literally generations ahead, continued to defeat their advances.  The same story is true for antivirals, such as Tamiflu (oseltamivir).  Multidrug-resistant bacteria and viruses are an increasing problem, especially in hospital settings.  Scientists are now looking to develop new methods, beyond standard antibiotics and antivirals, to combat bacterial and viral diseases.  Within the past month, many new treatments have been discussed, including the use of small interfering RNA (siRNA).

siRNA
There is currently no effective drug against the Ebola virus, but a new siRNA based method of treating the deadly Zaire Strain of the Ebola virus has proven successful in recent animal studies at the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID).  siRNAs are small pieces of RNA that block specific RNA sequences before they can be translated into a protein.  Because they are typically unstable, the researchers used a new method, developed by the Tekmira Pharmaceutical Corporation, to stabilize the siRNA for delivery.  This new delivery method could be easily modified and used to treat other viral hemorrhagic fevers or any other viral infections.  In fact, it may also be used to develop a broad spectrum treatment against the influenza virus.  Another research group has recently discovered a small viral RNA (svRNA) common to all influenza viruses that controls viral replication.  This svRNA could easily be targeted and destroyed by an siRNA. This breakthrough in treatment with siRNA offers hope to those who infected by previously untreatable infections, such as Ebola and other viral hemorrhagic fevers, or even by common viral infections, such as the influenza virus, that have developed resistance to standard antiviral medications.

These new advances in technology and basic science allow for targeted and broad spectrum treatments to an increasing number of antibiotic/antiviral-resistant pathogens.  Although these treatments may seem like modern “wonder drugs,” they can ultimately become resistant and ineffective.  Because many in the medical field have witnessed first-hand the rise and decline of antibiotic and antiviral effectiveness,  a more responsibility approach to the use of these new drugs will likely be taken in effort to delay the emergence of resistant pathogens.

While beneficial, all technological advances have the potential for misuse, and a continual effort to raise the awareness of these issues to scientists and the community is needed.  The FAS Biosecurity program’s dual use case studies highlight some research related to the topics mention in this post, including the “Antibiotic Resistance” and “RNA interference” case studies.

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2 Responses to “Future Treatment: siRNA”

  1. Atul Tyagi July 22, 2010 at 5:17 AM #

    Dear Sir,
    I have found one major problem of efficacy. I am sendind a paper link in which efficacy has given in log.i want to get efficacy but i don’t know any method about log.So would you tell me any method how to find out in log .i sending also pubmed id of this paper…………..

    JOURNAL OF VIROLOGY, Mar. 2004, p. 2601–2605
    pubmed id 14963165

  2. Kelsey Gregg July 22, 2010 at 11:13 AM #

    As observed in the Das AT, et al (2004) paper, HIV-1 is a particularly difficult disease to treat because it rapidly mutates and can overcome a variety treatment methods (both anti-virals and siRNA). Currently, Highly Active Antiretroviral Therapy (HAART) is used to treat HIV. The HAART method uses a variety of antivirals in combination, since the probability of a virus mutating to overcome 3 or 4 treatments at once is much less than overcoming only one treatment. The study concludes that siRNA treatments “… could become a realistic gene therapy approach with which to overcome the devastating effect of HIV-1 on the immune system.” But, “…antiviral approaches involving RNAi should be used in a combined fashion to prevent the emergence of resistant viruses.”

    As per efficacy of siRNA treatment, it depends on the target gene and, over time, the adaptability of the target organism. The paper only showed data for cultured cells, the efficacy of treatment in humans would be different. Some figures were on a log scale, but you can still take the approximate value of the virus load and compare them in any way you wish. Here is a simple example of logarithmic scales: http://www.ieer.org/clssroom/log.html

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