Navigation Links
Seamless gene correction of beta-thalassemia mutations in patient-specific cells
Date:8/5/2014

August 5, 2014 A major hurdle in gene therapy is the efficient integration of a corrected gene into a patient's genome without mutating off-target sites. In a paper published today in Genome Research, scientists have used CRISPR/Cas genome editing technology to seamlessly and efficiently correct disease-causing mutations in cells from patients with β-thalassemia.

β-thalassemia results from inherited DNA mutations in the hemoglobin beta (HBB) gene, resulting in reduced HBB expression in red blood cells and, in the most severe forms, anemia. The only established curative treatment is hematopoietic stem cell transplantation; however, this treatment requires a matched donor. Gene therapy, which delivers a corrected copy of a gene into patient cells, could bypass the need for a donor. Previous attempts using a virus to randomly insert a normal gene into the genome has been successful in one β-thalassemia patient, but the long-term effect of viral insertion is not yet known.

To correct HBB mutations directly in a patient's genome, researchers first generated induced pluripotent stem cells, or iPSCs, from skin cells of patients. The real breakthrough came when they applied CRISPR/Cas9 to precisely engineer a double strand DNA break at the HBB locus in these cells, allowing a donor plasmid with the corrected sites to be efficiently integrated, thus replacing the mutated sites. The donor plasmid also contained selectable markers to identify cells with corrected copies of the gene. These selectable markers were subsequently removed with transposase and a second round of selection, generating a seamless, corrected version of HBB in the patient's genome.

Importantly, the researchers could differentiate the corrected iPSCs into mature blood cells, and these blood cells showed restored expression of hemoglobin. However, much work is needed before these cells could be transplanted back into a patient for treating β-thalassemia. "Although we and others are able to differentiate iPSCs into blood cell progenitors as well as mature blood cells, the transplantation of the progenitors into mouse models to test them has so far proven very difficult," said senior author Yuet Wai Kan from the University of California, San Francisco. "I believe it will take quite a few more years before we can apply it in a clinical setting."


'/>"/>

Contact: Peggy Calicchia
calicchi@cshl.edu
516-422-4012
Cold Spring Harbor Laboratory
Source:Eurekalert  

Related biology technology :

1. Researchers advance scheme to design seamless integrated circuits etched on graphene
2. Rigaku publishes new WDXRF Application: Determination of Metals in Copper Concentrate by Advanced Correction Method for Fused Beads
3. Correction: Amarantus BioSciences Updates Shareholders on Timing of Michael J. Fox Foundation Grant Data Release
4. Sangamo BioSciences Announces First Presentation Of Data From ZFP Therapeutic Program For Treatment Of Sickle Cell Disease And Beta-Thalassemia At American Society Of Hematology Meeting
5. deCODE genetics Uncovers Impact of Mutations in The Human Genome on Cognitive Ability
6. Annai Systems to Support International Challenge to Improve the Detection of Cancer Mutations
7. QIAGEN Announces Partnership With Clovis Oncology to Co-develop Companion Diagnostic Targeting Drug-Resistant EGFR Mutations
8. Spartan Bioscience Receives FDA Clearance for First Rapid DNA Test of Mutations Affecting Metabolism of Common Drugs
9. Mutations in VCP gene implicated in a number of neurodegenerative diseases
10. Whole Genome Sequencing of Triple Negative Breast Cancer Reveals Previously Unreported Mutations
11. Autism mutations, scattered across many genes, merge into common network of interactions
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Seamless gene correction of beta-thalassemia mutations in patient-specific cells
(Date:6/23/2016)... - FACIT has announced the creation of a ... Propellon Therapeutics Inc. ("Propellon" or "the Company"), to ... of first-in-class WDR5 inhibitors for the treatment of ... an exciting class of therapies, possessing the potential ... patients. Substantial advances have been achieved with the ...
(Date:6/23/2016)... , June 23, 2016 Houston Methodist ... the Cy-Fair Sports Association to serve as their ... agreement, Houston Methodist Willowbrook will provide sponsorship support, ... connectivity with association coaches, volunteers, athletes and families. ... the Cy-Fair Sports Association and to bring Houston ...
(Date:6/23/2016)... June 23, 2016  The Prostate Cancer Foundation (PCF) is pleased ... and faster cures for prostate cancer. Members of the Class of 2016 were ... Read More About the Class of 2016 PCF Young ... ... ...
(Date:6/23/2016)... FRANCISCO , June 23, 2016   EpiBiome ... has secured $1 million in debt financing from Silicon ... ramp up automation and to advance its drug development ... its new facility. "SVB has been an ... beyond the services a traditional bank would provide," said ...
Breaking Biology Technology:
(Date:6/2/2016)... , June 2, 2016 The Department ... has awarded the 44 million US Dollar project, for the ... Vehicle Plates including Personalization, Enrolment, and IT Infrastructure , ... in the production and implementation of Identity Management Solutions. Numerous ... however Decatur was selected for the ...
(Date:6/1/2016)... NEW YORK , June 1, 2016 ... Biometric Technology in Election Administration and Criminal Identification to ... According to a recently released TechSci Research report, " ... Sector, By Region, Competition Forecast and Opportunities, 2011 - ... $ 24.8 billion by 2021, on account of growing ...
(Date:5/16/2016)... May 16, 2016   EyeLock LLC , a ... the opening of an IoT Center of Excellence in ... expand the development of embedded iris biometric applications. ... of convenience and security with unmatched biometric accuracy, making ... aside from DNA. EyeLock,s platform uses video technology to ...
Breaking Biology News(10 mins):