Publications

Progress Toward Treating Sickle Cell Disease with CRISPR-Cas9

Our lab, in collaboration with globinopathy experts and sickle cell clinicians, have taken a key step toward a cure for sickle cell disease (SCD), using CRISPR-Cas9...

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Our lab, in collaboration with globinopathy experts and sickle cell clinicians, have taken a key step toward a cure for sickle cell disease (SCD), using CRISPR-Cas9 genome engineering technology to reverse the disease-causing gene in stem cells from the blood of affected patients. For the first time, the genetic modification occurs in a sufficient proportion of stem cells to produce a substantial benefit in sickle cell patients. SCD primarily afflicts those of African descent and leads to anemia, painful blood blockages, and early death.

In collaboration with the UCSF Benioff Children’s Hospital Oakland Research Institute (CHORI) and the University of Utah School of Medicine, we showed that edited cells persist when transplanted into mice, an important factor in developing a lasting therapy. We’re aiming to improve the efficiency of their approach and perform large-scale studies in mice before attempting it in humans. Our lab hopes to work with Dr. Mark Walters, MD, an expert in curative treatments for sickle cell disease (such as bone marrow transplant and gene therapy), to design and initiate an early-phase clinical trial to test this new treatment within the next five years. Eventually, we hope to re-infuse patients with edited stem cells in order to alleviate symptoms of sickle cell disease.

Selection-Free Genome Editing of the Sickle Cell Mutation in Human Adult Hematopoietic Stem/Progenitor Cells  
Science Translational Medicine | Mark A. DeWitt, et al | October 12, 2016

 

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Sickle hemoglobin polymerizes under low oxygen tensions in the tissues and the red blood cell deforms, which leads to obstruction in the capillaries and painful episodes for the patients
Photo Credit: Frans Kuypers, PhD. RBClab.com, UCSF Benioff Children’s Hospital Oakland

 

Press Coverage

CRISPR deployed to combat sickle-cell anaemia: Studies in mice highlight the promises — and challenges — of CRISPR–Cas9 gene editing  
Nature | Heidi Ledford | October 12, 2016

3 Gene Editing Approaches for Sickle Cell Disease  
PLoS Blogs | Ricki Lewis | October 13, 2016

CRISPR edits sickle cell mutation: Edited blood stem cells could someday help patients produce healthy red blood cells  
Chemical and Engineering News | Ryan Cross | October 12, 2016

A new gene-editing technique could help treat sickle cell anemia: Scientists hope to have a clinical trial in the next five years  
The Verge | Angela Chen | October 12, 2016

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Next generation guide RNAs for genome-wide CRISPR screens

IGI Co-Director Jonathan Weissman, Scientific Director Jacob Corn, Research Scientist Chong Park, and other colleagues have developed the next generation...

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IGI Co-Director Jonathan Weissman, Scientific Director Jacob Corn, Research Scientist Chong Park, and other colleagues have developed the next generation of guide RNAs (gRNAs) for high-throughput CRISPR screens. Establishing rules for the design of effective gRNAs is critical to making CRISPR activation and repression screens more specific and robust. Based on recent observations that compacted DNA inhibits Cas9 access, the team modified their guide RNA design algorithm to target more open, expanded regions of human and mouse genomes. Taking chromatin, position, and sequence features into account allowed for the design of highly active guide RNA libraries.

gRNA library design tools are available on Github.  The improved gRNA libraries will soon be available on AddGene.

Compact and highly active next-generation libraries for CRISPR-mediated gene repression and activation  
eLife | Jonathan Weissman, Jacob Corn, Chong Park, et al | September 23, 2016

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IGI researchers increase CRISPR-Cas9 efficiency

IGI Researchers have discovered a way to increase the efficiency with which CRISPR-Cas9 technology cuts and disables genes in cells.  In culture, “knockout”...

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IGI Researchers have discovered a way to increase the efficiency with which CRISPR-Cas9 technology cuts and disables genes in cells.  In culture, “knockout” cell lines allow researchers to better understand the role of genetic information, and may eventually improve therapies for human genetic diseases.  

Non-homologous DNA increases gene disruption efficiency by altering DNA repair outcomes
Nature Communications | Chris Richardson, Jacob Corn, et al | August 17, 2016

Press Release
CRISPR-Cas9 breaks genes better if you disrupt DNA repair
UC Berkeley News | Robert Sanders | August 17, 2016

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IGI Researchers Improve Efficiency of CRISPR-Cas9 DNA repair

IGI researchers have recently made significant strides in improving the efficiency of CRISPR-Cas9 technology, as well as our understanding of its versatility...

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IGI researchers have recently made significant strides in improving the efficiency of CRISPR-Cas9 technology, as well as our understanding of its versatility in repairing genetic information within a cell.  In a paper published today in the journal Nature Biotechnology, IGI Scientific Director, Jacob Corn, and IGI postdoc Chris Richardson reveal that they have invented a new approach that improves the patching efficiency of Cas9-induced DNA breaks.  The new technique allows researchers to patch a section of DNA by inserting different genetic information,  and it is especially useful when trying to repair genetic mutations that cause hereditary diseases such as sickle cell disease or severe combined immune deficiency.  The precision of CRISPR-Cas9 technology in cutting DNA at precise locations has propelled a revolution in genetic engineering worldwide.  The process of making exact and accurate changes to the genetic code after a DNA break, however, has proved to be a much more challenging process, but this new approach will enable researchers to more efficiently alter the genetic code by using CRISPR-Cas9 technology to accurately insert new genetic information into the break.

Enhancing homology-directed genome editing by catalytically active and inactive CRISPR-Cas9 using asymmetric donor DNA 
Nature Biotechnology | Chris Richardson, Jacob Corn, et al | January 20, 2016

Press Release: Advance improves cutting and pasting with CRISPR-Cas9 gene editing
UC Berkeley News | Robert Sanders | January 20, 2016

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Questions and/or comments about Corn Lab and its activities may be addressed to:

JACOB.CORN@BIOL.ETHZ.CH

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