Navigation Links
Enhancing RNA interference
Date:6/24/2013

CAMBRIDGE, Mass. Nanoparticles that deliver short strands of RNA offer a way to treat cancer and other diseases by shutting off malfunctioning genes. Although this approach has shown some promise, scientists are still not sure exactly what happens to the nanoparticles once they get inside their target cells.

A new study from MIT sheds light on the nanoparticles' fate and suggests new ways to maximize delivery of the RNA strands they are carrying, known as short interfering RNA (siRNA).

"We've been able to develop nanoparticles that can deliver payloads into cells, but we didn't really understand how they do it," says Daniel Anderson, the Samuel Goldblith Associate Professor of Chemical Engineering at MIT. "Once you know how it works, there's potential that you can tinker with the system and make it work better."

Anderson, a member of MIT's Koch Institute for Integrative Cancer Research and MIT's Institute for Medical Engineering and Science, is the leader of a research team that set out to examine how the nanoparticles and their drug payloads are processed at a cellular and subcellular level. Their findings appear in the June 23 issue of Nature Biotechnology. Robert Langer, the David H. Koch Institute Professor at MIT, is also an author of the paper.

One RNA-delivery approach that has shown particular promise is packaging the strands with a lipidlike material; similar particles are now in clinical development for liver cancer and other diseases.

Through a process called RNA interference, siRNA targets messenger RNA (mRNA), which carries genetic instructions from a cell's DNA to the rest of the cell. When siRNA binds to mRNA, the message carried by that mRNA is destroyed. Exploiting that process could allow scientists to turn off genes that allow cancer cells to grow unchecked.

Scientists already knew that siRNA-carrying nanoparticles enter cells through a process, called endocytosis, by which cells engulf large molecules. The MIT team found that once the nanoparticles enter cells they become trapped in bubbles known as endocytic vesicles. This prevents most of the siRNA from reaching its target mRNA, which is located in the cell's cytosol (the main body of the cell).

This happens even with the most effective siRNA delivery materials, suggesting that there is a lot of room to improve the delivery rate, Anderson says.

"We believe that these particles can be made more efficient. They're already very efficient, to the point where micrograms of drug per kilogram of animal can work, but these types of studies give us clues as to how to improve performance," Anderson says.

Molecular traffic jam

The researchers found that once cells absorb the lipid-RNA nanoparticles, they are broken down within about an hour and excreted from the cells.

They also identified a protein called Niemann Pick type C1 (NPC1) as one of the major factors in the nanoparticle-recycling process. Without this protein, the particles could not be excreted from the cells, giving the siRNA more time to reach its targets. "In the absence of the NPC1, there's a traffic jam, and siRNA gets more time to escape from that traffic jam because there is a backlog," says Gaurav Sahay, an MIT postdoc and lead author of the Nature Biotechnology paper.

In studies of cells grown in the lab without NPC1, the researchers found that the level of gene silencing achieved with RNA interference was 10 to 15 times greater than that in normal cells.

Lack of NPC1 also causes a rare lysosomal storage disorder that is usually fatal in childhood. The findings suggest that patients with this disorder might benefit greatly from potential RNA interference therapy delivered by this type of nanoparticle, the researchers say. They are now planning to study the effects of knocking out the NPC1 gene on siRNA delivery in animals, with an eye toward testing possible siRNA treatments for the disorder.

The researchers are also looking for other factors involved in nanoparticle recycling that could make good targets for possibly slowing down or blocking the recycling process, which they believe could help make RNA interference drugs much more potent. Possible ways to do that could include giving a drug that interferes with nanoparticle recycling, or creating nanoparticle materials that can more effectively evade the recycling process.


'/>"/>

Contact: Sarah McDonnell
s_mcd@mit.edu
617-253-8923
Massachusetts Institute of Technology
Source:Eurekalert

Related medicine news :

1. Enhancing Compatibility and Boosting Performance; NEXCOM Introduces the ICES 670 COM Express Module Based on 4th Generation Intel® Core™ Processor
2. Research Suggests that Lack of Exercise Drive is Genetic, Making Energy Enhancing Supplements Like Prescopodene Beneficial For Sticking to Your Exercise Routine
3. NYU and NYU Langone researchers devise method for enhancing CEST MRI
4. Researchers identify new pathway, enhancing tamoxifen to tame aggressive breast cancer
5. BOMI International and Transwestern Partner to Offer Property and Facility Staff Skill-Enhancing Education Programs
6. Continuing Education Provider HomeCEUConnection.com Adds New Career Enhancing Video Courses to Online Catalog
7. Delray Recovery Center Treats Steroid and Performance Enhancing Drug Abuse
8. Astro Clairvoyant Norah Guide for Premium Astrology Announces Tools for Enhancing Inner Psychic Abilities in Blog Series
9. Enhancing breast cancer detection
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:4/29/2016)... Los Angeles, CA (PRWEB) , ... April 29, 2016 , ... ... Sarah Mirmelli, a mother and divorcee, shares her enthusiasm for Botox and lip injections, ... of the world famous youth oriented Coachella Valley Music and Arts Festival. The article ...
(Date:4/29/2016)... ... April 29, 2016 , ... Our bodies are bombarded daily ... confront and deal with these stressors is to adopt a more healthful diet, but ... you. Risa Groux, a certified Holistic Nutritionist and the creator of the Newport Beach ...
(Date:4/29/2016)... ... 2016 , ... The White House announced efforts yesterday to ... about their loan terms and accounts, and more protections for borrowers. The announcement ... private loans, has reached $1.3 trillion, with 43 million Americans holding student loans ...
(Date:4/29/2016)... , ... April 29, 2016 , ... Spine Team Texas, ... is proud to announce one of their physicians has been invited to be a ... (Texas ACOFP) Family Practice Review conference on April 30, 2016. , Dr. R. ...
(Date:4/29/2016)... ... April 29, 2016 , ... ... Celiac Association (CCA), is pleased to announce the launch of the GFCP ... articles, recipes, and more. The purpose of the GFCP Scoop site ...
Breaking Medicine News(10 mins):
(Date:4/29/2016)... , April 29, 2016 Glycotope ... expertise, today announces the appointment of Dr. Alfredo ... Zurlo is an oncologist with many years clinical experience ... biotechnology industries. His last role was at Mologen AG ... the Executive Board. Previously Dr. Zurlo held various positions ...
(Date:4/28/2016)... NEW YORK , April 28, 2016 /PRNewswire/ ... will notably complement the company,s valve repair and ... the move also places Abbott more firmly into ... one of the fastest growing device areas, with ... to its recent report,  Advanced Remote Patient ...
(Date:4/28/2016)... April 28, 2016 ... George Phillips und Stephen Schmidt ... ArisGlobal®, ein führender Anbieter cloudbasierter ... heute bekannt, dass neue Führungskräfte zum Team ... sind, die vielfältige Erfahrungen mitbringen.  Dies wird ...
Breaking Medicine Technology: