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 A Map of the Cell’s Power Station
18.08.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau

nachricht On the way to developing a new active ingredient against chronic infections
21.08.2017 | Deutsches Zentrum für Infektionsforschung

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

On the way to developing a new active ingredient against chronic infections

21.08.2017 | Life Sciences

Smart Computers

21.08.2017 | Information Technology

A Map of the Cell’s Power Station

18.08.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>