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 World’s Largest Study on Allergic Rhinitis Reveals new Risk Genes
17.07.2018 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

nachricht Plant mothers talk to their embryos via the hormone auxin
17.07.2018 | Institute of Science and Technology Austria

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: First evidence on the source of extragalactic particles

For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.

To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...

Im Focus: Magnetic vortices: Two independent magnetic skyrmion phases discovered in a single material

For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.

Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...

Im Focus: Breaking the bond: To take part or not?

Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.

A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...

Im Focus: New 2D Spectroscopy Methods

Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.

"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....

Im Focus: Chemical reactions in the light of ultrashort X-ray pulses from free-electron lasers

Ultra-short, high-intensity X-ray flashes open the door to the foundations of chemical reactions. Free-electron lasers generate these kinds of pulses, but there is a catch: the pulses vary in duration and energy. An international research team has now presented a solution: Using a ring of 16 detectors and a circularly polarized laser beam, they can determine both factors with attosecond accuracy.

Free-electron lasers (FELs) generate extremely short and intense X-ray flashes. Researchers can use these flashes to resolve structures with diameters on the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Leading experts in Diabetes, Metabolism and Biomedical Engineering discuss Precision Medicine

13.07.2018 | Event News

Conference on Laser Polishing – LaP: Fine Tuning for Surfaces

12.07.2018 | Event News

11th European Wood-based Panel Symposium 2018: Meeting point for the wood-based materials industry

03.07.2018 | Event News

 
Latest News

Microscopic trampoline may help create networks of quantum computers

17.07.2018 | Information Technology

In borophene, boundaries are no barrier

17.07.2018 | Materials Sciences

The role of Sodium for the Enhancement of Solar Cells

17.07.2018 | Power and Electrical Engineering

VideoLinks
Science & Research
Overview of more VideoLinks >>>