Navigation Links
New genome-editing platform significantly increases accuracy of CRISPR-based systems
Date:4/25/2014

A next-generation genome editing system developed by Massachusetts General Hospital (MGH) investigators substantially decreases the risk of producing unwanted, off-target gene mutations. In a paper receiving online publication in Nature Biotechnology, the researchers report a new CRISPR-based RNA-guided nuclease technology that uses two guide RNAs, significantly reducing the chance of cutting through DNA strands at mismatched sites.

"This system combines the ease of use of the widely adopted CRISPR/Cas system with a dimerization-dependent nuclease activity that confers higher specificity of action," says J. Keith Joung, MD, PhD, associate chief for Research in the MGH Department of Pathology and senior author of the report. "Higher specificity will be essential for any future clinical use of these nucleases, and the new class of proteins we describe could provide an important option for therapeutic genome editing."

Engineered CRISPR-Cas nucleases genome-editing tools that combine a short RNA segment matching its DNA target with a DNA-cutting enzyme called Cas9 have been the subject of much investigation since their initial development in 2012. Easier to use than the earlier ZFN (zinc finger nuclease) and TALEN (transcription activator-like effector nuclease) systems, they have successfully induced genomic changes in several animal models systems and in human cells. But in a previous Nature Biotechnology paper published in June 2013, Joung's team reported that CRISPR-Cas nucleases could produce additional mutations in human cells, even at sites that differed from the DNA target by as much as five nucleotides.

To address this situation, the investigators developed a new platform in which the targeting function of Cas9 was fused to a nuclease derived from a well-characterized enzyme called Fokl, which only functions when two copies of the molecule are paired, a relationship called dimerization. This change essentially doubled the length of DNA that must be recognized for cleavage by these new CRISPR RNA-guided Fokl nucleases (RFNs), significantly increasing the precision of genome editing in human cells. Importantly, Joung and his colleagues also demonstrated that these new RFNs are as effective at on-target modification as existing Cas9 nucleases that target a shorter DNA sequence.

"By doubling the length of the recognized DNA sequence, we have developed a new class of genome -editing tools with substantially improved fidelity compared with existing wild-type Cas9 nucleases and nickases (enzymes that cleave a single DNA strand)," says Joung, an associate professor of Pathology at Harvard Medical School. The research team also has developed software enabling users to identify potential target sites for these RFNs and incorporated that capability into ZiFiT Targeter, a software package freely available at http://zifit.partners.org.


'/>"/>
Contact: Sue McGreevey
smcgreevey@partners.org
617-724-2764
Massachusetts General Hospital
Source:Eurekalert

Related medicine news :

1. An open platform revolutionizes biomedical-image processing
2. CFO 911 Solutions' Charles K. Dargan II, CEO, and Reid Dabney, Managing Director Have Been Added to the Financial Entrepreneur Platform ("FEP") of Merriman Capital, Inc., a Wholly Owned Subsidiary of Merriman Holdings, Inc. (OTCQX: MERR)
3. Dr. Alan Jenks Launches a New Platform Called iHealthology.com to Help People Stay Healthy
4. Acutrack integrates with Infusionsoft ecommerce platform
5. GCI Trading/GCI Forex/GCI Financial Introduces ECN trading On Its MetaTrader4 Trading Platform
6. M&A Technology Launches Genius Station, an Interactive Instructional Platform for Education
7. RWJF awards $1.9 million grant to PatientsLikeMe to create open research platform
8. CogniFit Launches its Online Brain Training Platform in Japanese
9. Connect the Doc Launches Real Patient Reviews to their Online Appointment Booking Platform in Vancouver, BC
10. SocialWellth Launches Consumer mHealth Open Network Platform
11. CEU360.com Leverages Online Learning Technology to Provide the Most Powerful Team Education Platform
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:9/20/2017)... (PRWEB) , ... September 20, 2017 , ... ... and Centers of Excellence (CoE) with the latest Artificial Intelligence (AI) thinking, announced ... presence offers quick and easy access to essential information that offers a more ...
(Date:9/20/2017)... ... September 20, 2017 , ... ... and commercialization, has just released a new white paper discussing the benefits ... than ever about medical device, pharmaceutical, and combination product organizations making sure ...
(Date:9/20/2017)... ... ... Compliancy Group is proud to announce that its proprietary ... long-time client pass their Department of Health and Human Services (HHS) Office for ... the help of the Compliancy Group's Audit Response Program™, not a single client ...
(Date:9/20/2017)... ... 20, 2017 , ... The Centers for Medicare and Medicaid Services (CMS) stated ... to using only Worksheet S-10 to distribute Disproportionate Share Hospital (DSH) Uncompensated Care Payments ... complimentary webinars on October 17, 2017 at 2 P.M. EST and uncover how ...
(Date:9/20/2017)... ... 20, 2017 , ... “RECYCLED Ezekiel's Plan for Freedom from ... from ADDICTION” is the creation of published author, Bill Miller. Bill Miller ... services, including more than a decade of addiction to prescription drugs. He ...
Breaking Medicine News(10 mins):
(Date:9/7/2017)... STOCKHOLM , Sept. 7, 2017 NuvoAir ... Air Smart Spirometer, announced today a partnership with Novartis Pharma ... partnership solidifies NuvoAir,s position as the leading mobile spirometry platform ... respiratory patients. ... spirometry test ...
(Date:9/6/2017)... , Sept. 6, 2017  Robert G. Szewc, ... Pinnacle Professional Member in recognition of his contributions to ... serves as a Nephrologist at the practice of Kidney ... medicine, kidney care and hypertension solutions. He has worked ... years of career experience, as well as expertise in ...
(Date:9/6/2017)... NeuroRx, a clinical stage biopharma company developing the first oral ... granted Fast Track status by the US Food and Drug ... by NRX-101 (D-cycloserine + lurasidone). The company will shortly begin ... targeting patients who are admitted to Emergency Departments with ASIB ... ...
Breaking Medicine Technology: