Navigation Links
Sanford-Burnham researchers develop novel nanoparticle to deliver powerful RNA interference drugs
Date:7/9/2013

LA JOLLA, Calif., July 8 2013 Silencing genes that have malfunctioned is an important approach for treating diseases such as cancer and heart disease. One effective approach is to deliver drugs made from small molecules of ribonucleic acid, or RNA, which are used to inhibit gene expression. The drugs, in essence, mimic a natural process called RNA interference.

In a new paper appearing today online in the journal, ACS Medicinal Chemistry Letters, researchers at Sanford-Burnham Medical Research Institute have developed nanoparticles that appear to solve a big challenge in delivering the RNA molecules, called small interfering RNA, or siRNA, to the cells where they are needed. By synthesizing a nanoparticle that releases its siRNA cargo only after it enters targeted cells, Dr. Tariq M. Rana and colleagues showed in mice that they could deliver drugs that silenced the genes they wanted.

"Our study describes a strategy to reduce toxic effects of nanoparticles, and deliver a cargo to its target," said Dr. Rana, whose paper, "In Vivo Delivery of RNAi by Reducible Interfering Nanoparticles (iNOPs)," also included contributions from researchers at the University of Massachusetts Medical School and the University of California at San Diego. "We've found a way to release the siRNA compounds, so it can be more effective where it's needed," Dr. Rana said.

In their experiment, the team synthesized what they call interfering nanoparticles, or iNOPs, made from repetitively branched molecules of a small natural polymer called poly-L-lysine. The iNOPs were specially designed with positively charged residues connected by disulfide bonds and these iNOPS assemble into a complex with negatively charged siRNA molecules. It's the bonds that ensure that the siRNA molecules remain with the nanoparticle, named iNOP-7DS. However, once inside targeted cells, a naturally occurring and abundant antioxidant called glutathione breaks the bond, releasing the siRNA molecules. In their experiment, Dr. Rana and colleagues showed in the lab that iNOP-7DS is reducible that is, the disulfide bonds holding the siRNA molecules can be broken.

They next showed that iNOP-7DS can be delivered effectively inside cultured murine liver cells, where the siRNA molecules silenced a gene called ApoB. This gene has been notoriously difficult to regulate in liver cells with small molecule drugs; high levels of the protein that ApoB encodes can lead to plaques that cause vascular disease.

Dr. Rana's lab further showed in tests that their nanoparticle remained stable in serum, suggesting that it is not degraded in the bloodstream. Finally, the researchers showed in tests with mice that their nanoparticle iNOP-7DS can be delivered effectively to the liver, spleen, and lung; and it suppressed the level of messenger RNA involved in the expression of the ApoB gene. In their in vivo experiment, they found that extremely small doses of siRNA were effective.

The next step, Dr. Rana said, is to increase the efficacy of iNOP-7DS in other in vivo experiments. "We would like to target not only ApoB, but cancer causing genes as well and in other tissues. That is the next goal." By marshaling the naturally occurring phenomenon of RNA interference, scientists are developing new ways to silence errant gene expression involved in illnesses. The nanoparticles developed by Dr. Rana and colleagues offer a potential new strategy for delivering this powerful therapeutic approach.


'/>"/>

Contact: Deborah Robison
drobison@sanfordburnham.org
407-615-0072
Sanford-Burnham Medical Research Institute
Source:Eurekalert

Related medicine news :

1. Sanford-Burnham collaborates with 5 Florida-based research organizations
2. Sanford-Burnhams Erkki Ruoslahti named to Thomson Reuters Nobel Prize watch list
3. Researchers investigate mechanism of Alzheimers therapy
4. Researchers pinpoint sources of fibrosis-promoting cells that ravage organs
5. Researchers use immunocytochemistry to determine ALK status
6. Researchers find 2 new methods to determine ALK status
7. CWRU researchers trace inner-city womens health issues to childhood traumas
8. Penn Medicine researchers discover link between fear and sound perception
9. UCI researchers awarded $2.27 million to create novel diabetes treatments
10. MS researchers determine that brain reserve independently protects against cognitive decline in MS
11. Notre Dame and Harper researchers developing novel method to test for HPV and oral cancers
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:12/2/2016)... ... December 02, 2016 , ... ... two ostomy patients, standing as living proof that attitude and determination can combine ... and issues that spike around the holidays. This campaign will offer patients a ...
(Date:12/2/2016)... ... December 02, 2016 , ... Mediaplanet is proud to ... which covers the innovative treatments, therapeutic technologies, and revolutionized nutrition that are helping ... prolonging life 6 years in the last 3 decades,” says Dr. Valentine Fuster, ...
(Date:12/2/2016)... ... December 02, 2016 , ... Universal Medical Systems, Inc. ... the first company to offer robotic imaging to veterinary medicine is sponsoring the ... 941 for the American Association of Equine Practitioners 62nd Annual Convention from December ...
(Date:12/2/2016)... ... ... Yisrayl Hawkins, at The House of Yahweh in Abilene, Texas, has published ... Yisrayl says this generation, known as the Last Generation, started in 1934 A.Y. (After ... up exactly with Bible Prophecy – a protected way for those who will believe. ...
(Date:12/2/2016)... ... December 02, 2016 , ... On ... individuals and families from eight different sites throughout Miami-Dade and Broward counties. This ... volunteers worked very hard on Thanksgiving morning by putting together individual meals via ...
Breaking Medicine News(10 mins):
(Date:12/2/2016)... National Pharmacy Services, LLC ("Maxor"), today announced that it has ... of Texas -based Maxor Specialty / IV ... both company,s clinical expertise and high-touch patient service models to ... About Maxor ... , , Established ...
(Date:12/2/2016)... , Dec. 2, 2016 Boston Scientific Corporation ... agreement to acquire certain manufacturing assets and capabilities of ... NVC) advanced biological tissue business, as well as a ... $75 million in cash. The Neovasc advanced biological tissue ... the Boston Scientific Lotus™ Valve System. * Upon ...
(Date:12/2/2016)... N.J. , Dec. 2, 2016   CytoSorbents ... immunotherapy leader commercializing its European Union approved CytoSorb ... and cardiac surgery patients worldwide, announced that Dr. ... the 9th Annual LD Micro Main Event ... , 2016 at the Luxe Sunset Boulevard Hotel in ...
Breaking Medicine Technology: