Navigation Links
New RNA interference technique can silence up to 5 genes
Date:12/28/2009

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
jfhirsch@mit.edu
617-253-1682
Massachusetts Institute of Technology
Source:Eurekalert

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:
*Name:
*Comment:
*Email:
(Date:1/6/2017)...  Delta ID Inc., a leader in consumer-grade iris ... at CES® 2017. Delta ID has collaborated with Gentex ... use of iris scanning as a secure, reliable and ... a car, and as a way to elevate the ... Delta ID and Gentex will demonstrate (booth #7326 LVCC) ...
(Date:12/22/2016)...  As part of its longstanding mission to improve genetic ... recently released its latest children,s book, titled The ... the topics of inheritance and variation of traits that are ... elementary school classrooms in the US. The ... Ariana Killoran , whose previous book with 23andMe, ...
(Date:12/19/2016)... 19 de diciembre de 2016  Mosaic Biomedicals SL anunció hoy ... de MSC-1, un anticuerpo humanizado que se espera comenzar a utilizar ... múltiples sitios previstos a lo largo de Europa y Norteamérica. ... MSC-1 es el primer ... leucemia (LIF), una citoquina pleiotrópica que se sobreexpresa en ciertos tumores ...
Breaking Biology News(10 mins):
(Date:1/20/2017)... Ginkgo Bioworks, the organism company, announced ... the synthesis and assembly of DNA. The acquisition ... synthetic DNA into Ginkgo,s automated organism engineering foundries, ... of new organism designs for application across a ... founded to significantly increase the world,s capacity to ...
(Date:1/20/2017)... (PRWEB) , ... January 20, ... ... in Less Exposure Surgery (LES®) Technologies, announced today the next evolution in ... Pedicle Screw System platform). In contrast to the competition, SpineFrontier is focused ...
(Date:1/19/2017)...  Market Research Future has a half cooked research report on ... growing rapidly and expected to reach USD 450 Million by the ... ... has been assessed as a swiftly growing market and expected that ... coming future. There has been a tremendous growth in the prevalence ...
(Date:1/19/2017)... , Jan. 19, 2017 /PRNewswire -- WuXi ... device open-access capability and technology platform, today announced ... leading biology focused preclinical drug discovery contract research ... will become a wholly-owned subsidiary of WuXi, and ... competences and providing greater services. The acquisition will ...
Breaking Biology Technology: