Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Disease knowledge may advance faster with CRISPR gene probing tool

08.03.2013
New technology can turn off genes more precisely, UCSF researchers say

Scientists at UC San Francisco have found a more precise way to turn off genes, a finding that will speed research discoveries and biotech advances and may eventually prove useful in reprogramming cells to regenerate organs and tissues.

The strategy borrows from the molecular toolbox of bacteria, using a protein employed by microbes to fight off viruses, according to the researchers, who describe the technique in the current issue of Cell.

Turning off genes is a major goal of treatments that target cancer and other diseases. In addition, the ability to turn genes off to learn more about how cells work is a key to unlocking the mysteries of biochemical pathways and interactions that drive normal development as well as disease progression.

"We've spent energy and effort to map the human genome, but we don't yet understand how the genetic blueprint leads to a human being, and how we can manipulate the genome to better understand and treat disease," said Wendell Lim, PhD, a senior author of the study. Lim is director of the UCSF Center for Systems and Synthetic Biology, a Howard Hughes Medical Investigator and professor of cellular and molecular pharmacology.

The new technology developed by the team of UCSF and UC Berkeley researchers is called CRISPR interference – not to be confused with RNA interference, an already popular strategy for turning off protein production.

"CRISPR interference is a simple approach for selectively perturbing gene expression on a genome-wide scale," said Lei Stanley Qi, PhD, a UCSF Systems Biology Fellow who was the lead author of the Cell study. "This technology is an elegant way to search for any short DNA sequence in the genome, and to then control the expression of the gene where that sequence is located."

The technique will allow researchers to more easily and accurately trace patterns of gene activation and biochemical chains of events that take place within cells, Qi said, and will help scientists identify key proteins that normally control these events and that may go awry in disease.

Unlike conventional RNA interference techniques, CRISPR interference allows any number of individual genes to be silenced at the same time, Qi said. In addition, it acts more crisply, if you will, by not turning off untargeted genes the way RNA interference techniques do.

Gene switching by RNA interference was identified more than a decade ago, launching a new research field that has spawned a Nobel Prize and billion-dollar biotech firms. In January, the U.S. Food and Drug Administration announced its first approval of an injectable disease therapy based on a similar interference strategy, a drug to treat a rare form of high cholesterol.

RNA interference blocks the messenger RNA that drives protein protection based on the blueprint contained within a gene's DNA sequence. By preventing protein production, RNA interference may be used to get around the problem of difficult-to-target proteins, a frequent challenge in drug development.

But CRISPR interference acts one step earlier in the cell's protein manufacturing process. "The horse has already left the barn with RNA interference, in the sense that the RNA message already has been transcribed from DNA," said Jonathan Weissman, PhD, a Howard Hughes Medical Investigator and professor of cellular and molecular pharmacology, who is another senior author on the work. "With CRISPR interference, we can prevent the message from being written."

CRISPR – an acronym for "clustered regularly interspaced short palindromic repeats" – is a system that bacteria use to defend themselves against viruses. CRISPR acts like a vaccine, incorporating bits of genes from viruses. Bacteria can reference this library of virus genes to recognize and attack viral invaders.

Qi and colleagues used a protein from this system, called Cas9, as a chassis into which they can insert any specific RNA partner molecule. The selected RNA serves as an adaptor that determines the target anywhere within the genome. "Targeting the machinery to new sites is extremely flexible and quick," Qi said.

The research team was able to get the system to work in mammalian cells as well as bacterial cells, and is working to improve its efficiency in mammalian cells, including human cells. The team aims to couple the Cas9 chassis to an enzyme that will enable the technology to turn genes on as well as off.

Such a versatile tool could prove valuable in efforts to reprogram cells for regenerative medicine. Lim's own lab is working on reprogramming immune cells to treat cancer.

"The idea is to reprogram cells to do the things we want them to do," Lim said. "We are still unlocking the secrets of the genome to harness the power of cellular reprogramming."

Additional UCSF co-authors of the February 28 Cell study are postdoctoral fellows Matthew Larson, PhD, and Luke Gilbert, PhD. UC Berkeley co-authors are Adam Arkin, PhD, professor of bioengineering; and Jennifer Doudna, PhD, Howard Hughes Medical Investigator and professor of biochemistry. All the study authors are members of QB3, the California Institute for Quantitative Biosciences.

The research was funded by the National Institutes of Health, the Howard Hughes Medical Institute and the National Science Foundation.

UCSF is a leading university dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care.

Jeffrey Norris | EurekAlert!
Further information:
http://www.ucsf.edu

More articles from Life Sciences:

nachricht The birth of a new protein
20.10.2017 | University of Arizona

nachricht Building New Moss Factories
20.10.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Neutron star merger directly observed for the first time

University of Maryland researchers contribute to historic detection of gravitational waves and light created by event

On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...

Im Focus: Breaking: the first light from two neutron stars merging

Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.

Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....

Im Focus: Smart sensors for efficient processes

Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).

When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...

Im Focus: Cold molecules on collision course

Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.

How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...

Im Focus: Shrinking the proton again!

Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.

It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ASEAN Member States discuss the future role of renewable energy

17.10.2017 | Event News

World Health Summit 2017: International experts set the course for the future of Global Health

10.10.2017 | Event News

Climate Engineering Conference 2017 Opens in Berlin

10.10.2017 | Event News

 
Latest News

Terahertz spectroscopy goes nano

20.10.2017 | Information Technology

Strange but true: Turning a material upside down can sometimes make it softer

20.10.2017 | Materials Sciences

NRL clarifies valley polarization for electronic and optoelectronic technologies

20.10.2017 | Interdisciplinary Research

VideoLinks
B2B-VideoLinks
More VideoLinks >>>