What are siRNA approaches to cure diseases??

Question

What are siRNA approaches to cure diseases??

Answer 1

HD Lighthouse Contributing Editor's Comment: Interference with messenger RNA is a way to silence the HD gene, the root cause of Huntington's Disease. If a safe and effective technology to do this can be developed, it would prevent the disease from developing in the presymptomatic. Research with mouse models also suggests that it would be a major treatment for those who have already developed the disease. In addition, research in conditional mouse models has shown that turning off the gene results in actual improvement even well into the disease process.

Different research teams have been working on different technologies for delivery and for RNA interference itself. There are many details to work out to achieve a safe and efficient RNAi therapy. The promise of RNAi is so great, not just for Huntington's but for many other diseases, that the research has moved beyond the university laboratory and into the pharmaceutical companies.

Two leaders in the development of RNA therapeutics for HD are Sirna Therapeutics (acquired last year by Merck) and Alnylam Pharmaceuticals. Sirna is working with Dr. Beverly Davidson. Alnylam is working with a team of researchers at the University of Massachusetts. The Lighthouse recently covered research on the safety of Alnylam's technology by a different group of researchers (see http://www.hdlighthouse.org/showUpdate.p...

The report below is from the University of Massachusetts team. It involves different technologies and a different mouse model. Cholesterol conjugated short interfering RNA duplexes were introduced through an adenoviral vector with a single injection.

The mouse model was created by introducing mutant huntingtin's protein fragments through the same viral vector that introduced the short interfering RNA duplexes. This model has the advantage of inducing disease pathology within two weeks.

The single RNAi injection protected striatal neurons, reduced the size and number of aggregates and resulted in less abnormal behavior than the control group. The injection did not cause inflammation.

The report concludes, "The next challenge in testing siRNA therapeutics in brain disease will be the delivery of small RNAs to maximize target specificity, with the capacity to distinguish between mutant and wild-type alleles."