Navigation Links
New RNA interference technique can silence up to 5 genes

CAMBRIDGE, Mass. Researchers at MIT and Alnylam Pharmaceuticals report this week that they have successfully used RNA interference to turn off multiple genes in the livers of mice, an advance that could lead to new treatments for diseases of the liver and other organs.

Since the 1998 discovery of RNA interference the naturally occurring phenomenon in which the flow of genetic information from a cell's nucleus to the protein-building machinery of the cell is disrupted scientists have been pursuing the tantalizing ability to shut off any gene in the body. Specifically, they have been trying to silence malfunctioning genes that cause diseases such as cancer.

The new delivery method, described in the Proceedings of the National Academy of Sciences, is orders of magnitude more effective than previous methods, says Daniel Anderson, senior author of the paper and a biomedical engineer at the David H. Koch Institute for Integrative Cancer Research at MIT.

"This greatly improved efficacy allows us to dramatically decrease the dose levels, and also opens the door to formulations that can simultaneously inhibit multiple genes or pathways," says Anderson.

The key to success with RNA interference is finding a safe and effective way to deliver the short strands of RNA that can bind with and destroy messenger RNA, which carries instructions from the nucleus.

Anderson and his colleagues believe the best way to do that is to wrap short interfering RNA (siRNA) in a layer of fat-like molecules called lipidoids, which can cross cells' fatty outer membrane. Using one such lipidoid, the researchers were able to successfully deliver five snippets of RNA at once, and Anderson believes the lipidoids have the potential to deliver as many as 20.

How they did it: The team at MIT, along with Alnylam researchers, have developed methods to rapidly produce, assemble and screen a variety of different lipidoids, allowing them to pick out the most effective ones.

In a previous study, the researchers created more than 1,000 lipidoids. For their latest study, they picked out one of the most effective and used a novel chemical reaction to create a new library of 126 similar molecules. The team focused on one that appeared the most promising, dubbed C12-200.

Using C12-200, the researchers achieved effective gene silencing with a dose of less than 0.01 milligrams of siRNA per kilogram of solution, and 0.01 milligrams per kilogram in non-human primates. If the same dosing were translated to humans, a potential therapy would only require an injection of less than 1 milliliter to specifically inhibit a gene, compared with previous formulations that would have required hundreds of milliliters, says Anderson.

Other authors from MIT include Kevin T. Love, Kerry P. Mahon, Christopher G. Levins, Kathryn A. Whitehead and Institute Professor Robert Langer.

Next steps: The MIT/Alnylam team hopes to start clinical trials within the next couple of years, after figuring out optimal doses and scaling up the manufacturing capability so they can produce large amounts of the siRNA-lipidoid complex.


Contact: Jen Hirsch
Massachusetts Institute of Technology

Related biology news :

1. RNA interference therapy heals growth deficiency disorder in a live animal
2. New source of classical techniques for blood-based studies in the laboratory mouse
3. New forensic technique gives clues about sharks from bite damage
4. Technique finds gene regulatory sites without knowledge of regulators
5. New neuroimaging analysis technique identifies impact of Alzheimers disease gene in healthy brains
6. Ancient penguin DNA raises doubts about accuracy of genetic dating techniques
7. UF scientists discover new explanation for controversial old patient-care technique
8. New nanochemistry technique encases single molecules in microdroplets
9. Breathing technique can reduce frequency, severity of asthma attacks
10. ORNL scientists hone technique to safeguard water supplies
11. Ben-Gurion U. developing new computer techniques to analyze historic Hebrew and Arabic documents
Post Your Comments:
(Date:11/12/2015)... Nov. 12, 2015  Arxspan has entered into ... and Harvard for use of its ArxLab cloud-based ... tools. The partnership will support the institute,s efforts ... chemical research information internally and with external collaborators. ... for managing the Institute,s electronic laboratory notebook, compound ...
(Date:11/9/2015)... DUBLIN , Nov. 09, 2015 /PRNewswire/ ... announced the addition of the "Global ... to their offering. --> ... "Global Law Enforcement Biometrics Market 2015-2019" ... Research and Markets ( ) ...
(Date:10/29/2015)... 2015  The J. Craig Venter Institute (JCVI) policy ... and Biosecurity: Lessons Learned and Options for the Future," ... Human Services guidance for synthetic biology providers has worked ... --> --> Synthetic biology promises ... to pose unique biosecurity threats. It now is easier ...
Breaking Biology News(10 mins):
(Date:11/30/2015)... ... 2015 , ... Imagine Exhibitions and Universal Partnerships & Licensing ... March 2016 at Melbourne Museum in Melbourne, Australia. Immediately following the Australia premiere, ... dates. The Exhibition is based on Universal Pictures’ Jurassic World, one of the ...
(Date:11/30/2015)... SAN DIEGO , Nov. 30, 2015 ... today that the company has acquired Cypher Genomics, Inc., ... and robust human genomic interpretation software solutions. The ... who will join HLI including Cypher CEO and Co-founder, ... head of HLI,s Pediatric Business.  Financial details of the ...
(Date:11/30/2015)... DIEGO , Nov. 30, 2015  HUYA Bioscience ... China,s pharmaceutical innovations, today announced it ... Drug Development Fund (KDDF) to foster collaboration between KDDF ... development and commercialization of healthcare products for the global ... as an important source of new innovative preclinical and ...
(Date:11/30/2015)... Ill. , Nov. 30, 2015  AbbVie, is ... program that focuses on a daily routine for managing ... take their medication can affect the way the body ... follow to their a daily routine are important. The ... to help patients better manage their hypothyroidism by establishing ...
Breaking Biology Technology: