Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

RNA-based drugs give more control over gene editing

17.11.2015

CRISPR/Cas9 gene editing technique can be transiently activated and inactivated using RNA-based drugs, giving researchers more precise control in correcting and inactivating genes

In just the past few years, researchers have found a way to use a naturally occurring bacterial system known as CRISPR/Cas9 to inactivate or correct specific genes in any organism. CRISPR/Cas9 gene editing activity runs continuously, though, leading to risk of additional editing at unwanted sites. Now, researchers at University of California, San Diego School of Medicine, Ludwig Cancer Research and Isis Pharmaceuticals demonstrate a commercially feasible way to use RNA to turn the CRISPR-Cas9 system on and off as desired -- permanently editing a gene, but only temporarily activating CRISPR-Cas9. The study is published November 16 by Proceedings of the National Academy of Sciences.


The conventional CRISPR-Cas9 system comprises two parts: the Cas9 enzyme, which acts like a wrench, and specific RNA guides (CRISPRs), which act as different socket heads. These RNAs guide the Cas9 protein to the target gene on a DNA strand. This technique allows researchers to study genes in a specific, targeted way.

Credit: Ernesto del Aguila III, NHGRI

"These findings provide a platform for multiple therapeutic applications, especially for nervous system diseases, using successive application of designer CRISPR RNA drugs," said senior author Don Cleveland, PhD, Distinguished Professor and Chair of the Department of Cellular and Molecular Medicine at UC San Diego School of Medicine and head of Ludwig Cancer Research's Laboratory for Cell Biology.

CRISPR/Cas9 works like this: researchers design a "guide" RNA to match the sequence of a specific target gene. The RNA guides the Cas9 enzyme to the desired spot, where it cuts the DNA. The cell can repair the DNA break, but it does so imprecisely, thereby inactivating the gene. Alternatively, researchers can coax the cell into replacing the section adjacent to the cut with a healthier version of the gene. Researchers are now testing the CRISPR/Cas9 system in a variety of applications to repair defective genes that cause disease.

The new approach introduces chemically modified, RNA-based drugs to transiently activate the CRISPR/Cas9 gene editing system. An initial, specially modified RNA is used to replace the usual guide RNA. This RNA directs Cas9's DNA-cutting activity to a selected target gene and the editing process proceeds. Activity is transient, however, as the editing stops when the guiding RNA drug is cleared. An extension of the approach can switch off the molecular scissors even faster by addition of a second, chemically modified RNA drug that directs inactivation of the gene encoding the Cas9 enzyme.

"The RNA-based drugs we developed in this study provide many advantages over the current CRISPR/Cas9 system, such as increased editing efficiency and potential selectivity," said Cleveland. "In addition, they can be synthesized efficiently, on an industrial scale and in a commercially feasible manner today."

"Today's published work is another demonstration of the successful synergy between Dr. Cleveland's lab and my team at Isis Pharmaceuticals," said C. Frank Bennet, PhD, co-senior author of the study and senior vice president of research at Isis Pharmaceuticals. "Leveraging Isis' expertise in developing RNA-targeted compounds, together the team has demonstrated that we can develop molecules that enhance the effectiveness of the CRISPR mechanism."

###

Study co-authors include Meghdad Rahdar, Thazha P. Prakash, Eric E. Swayze, Isis Pharmaceuticals; Moira A. McMahon, Ludwig Cancer Research and UC San Diego.

This research was funded, in part, by the National Institutes of Health (grants R01-GM 074150, R01-NS27036 and F32-GM109657). Cleveland is a paid consultant of Isis Pharmaceuticals.

Full study: http://doi.org/10.1073/pnas.1520883112

Media Contact

Heather Buschman
hbuschman@ucsd.edu
619-543-6163

 @UCSanDiego

http://www.ucsd.edu 

Heather Buschman | EurekAlert!

Further reports about: CRISPR Cas9 DNA Medicine RNA drugs enzyme industrial scale nervous system

More articles from Life Sciences:

nachricht New risk factors for anxiety disorders
24.02.2017 | Julius-Maximilians-Universität Würzburg

nachricht Stingless bees have their nests protected by soldiers
24.02.2017 | Johannes Gutenberg-Universität Mainz

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Stingless bees have their nests protected by soldiers

24.02.2017 | Life Sciences

New risk factors for anxiety disorders

24.02.2017 | Life Sciences

MWC 2017: 5G Capital Berlin

24.02.2017 | Trade Fair News

VideoLinks
B2B-VideoLinks
More VideoLinks >>>