Breakthrough in Silencing 'Bad' genes

[Mike Bartolatz]

Breakthrough in Silencing "Bad" Genes
Posted 03/31/2006

Anthony L. Komaroff, MD




Despite making great progress in identifying disease-causing genes, we still don't know how to turn them off. That's why biologists are so excited about a new tool for silencing bad genes, called RNA interference, or RNAi.[1]

We've known for 40 years how messenger RNA and related RNAs make particular proteins from particular genes. Within just the past 5 years, a new form of RNA, "microRNAs," has been discovered. Specific microRNAs silence the action of a particular gene in making a particular protein. They can be synthesized to silence any known gene, revolutionizing biological research.

RNA interference also already is leading to new treatments. For example, in animal studies, RNAi has stifled several viral diseases, including genital herpes, viral hepatitis, and retroviral infections. In animals, it has also treated spinocerebellar ataxia and several types of cancer, and dramatically lowered cholesterol levels.[2] Last year, promising results were reported in human studies using microRNAs to treat macular degeneration. These small RNAs are easy and inexpensive to synthesize, and the immune system does not recognize them as foreign, making adverse effects less likely.

Work still needs to be done in delivering microRNAs to the cells deep inside the body, where the wayward genes are causing mayhem. But progress is being made, as shown by the animal and human studies: Tricks have been discovered already for protecting microRNAs from destruction as they circulate through the body, and for allowing them entry into the target cells.

RNA interference has little effect on practice today. Most knowledgeable authorities think it will have a profound effect tomorrow, and they define tomorrow as the next 10 years.

That's my opinion. I'm Dr. Anthony Komaroff, Professor of Medicine, Harvard Medical School.



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References
Dykxhoorn DM, Lieberman J. The silent revolution: RNA interference as basic biology, research tool, and therapeutic. Annu Rev Med. 2005;56:401-423. Abstract
Soutschek J, Akinc A, Bramlage B, et al. Therapeutic silencing of an endogenous gene by systemic administration of modified siRNAs. Nature. 2004;432:173.s




Anthony L. Komaroff, MD, Professor of Medicine, Harvard Medical School, Boston, Massachusetts. Email: komaroff@hms.harvard.edu


Disclosure: Anthony L. Komaroff, MD, has disclosed no relevant financial relationships.


Medscape General Medicine. 2006;8(1):88. ©2006 Medscape