Lab News

The management and research teams from Intellia Therapeutics came to visit UC Berkeley today. Thomas Barnes, Ph.D., the Senior Vice President of Innovative Sciences & eXtellia, and his teams shared their scientific expertise in CRISPR/Cas9 technology and clinical development experience to the members in Corn lab.

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Corn Lab post-doc Benjamin Gowen is attending the 2017 Immune Regulation in Autoimmunity and Cancer Keystone Conference in Whistler, British Columbia from March 26-30, 2017.  If you’re attending the meeting, you should come by poster #1030 to see his work on the discovery of an autoimmunity-associated IL2RA enhancer. 

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In February, Corn Lab post-doc Benjamin Gowen traveled to Australia to visit collaborators at the Commonwealth Scientific and Industrial Research Organisation and  present his research at the 2017 Lorne Genome Conference. His talk was titled “Discovery of an autoimmunity-associated IL2RA enhancer by unbiased targeting of transcriptional activation” and featured work by members of the Corn Lab and Alex Marson’s lab at UCSF.

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The Corn lab and our collaborators have received a $4 million grant from the California Institute for Regenerative Medicine (CIRM) to develop CRISPR-Cas9 genome engineering into a cure for sickle cell disease (SCD).

This generous funding will support the fruitful ongoing collaboration between our lab, physicians and sickle cell experts Mark Walters and David Martin of UCSF Benioff Children’s Hospital Oakland Research Institute (CHORI), and stem cell and gene therapy specialist Don Kohn of UCLA.  The grant is part of CIRM’s Translational Award program, which aims to move “the most promising projects out of the laboratory and into clinical trials in people.” 

We are very grateful for CIRM’s support, which enables us to establish clinical protocols for gene surgery to cure sickle cell disease. CRISPR cures for genetic diseases are rapidly approaching the clinic, and our research will lay the groundwork for a clinical trial in SCD. Our clinical approach will involve removing stem cells from the bone marrow of sickle cell patients, editing the mutated DNA code with CRISPR-Cas9, and putting the corrected cells back into the patient, where they can persist and spawn healthy red blood cells. 

We recently published proof-of-concept sickle gene editing in Science Translational Medicine, and the funding from CIRM will enable us to improve the efficiency of editing, scale up the process, and perform more extensive studies in animals to ensure safety and accuracy before moving into human clinical trials. Mark DeWitt, a postdoc in the lab and first author on the Science Translational Medicine paper, will become the project’s Program Manager, managing research across the three campuses.

For a more in-depth perspective, read Jacob’s blog post on deploying gene editing to tackle sickle cell disease.

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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

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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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 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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In this new article for the June issue of Discover Magazine, Jeff Wheelwright takes a tour of the Bay Area’s active biotech world, talking with a wide range of researchers – from high-school kids to global corporations – who are embracing CRISPR-Cas9 genetic engineering technology.

The Revolution Will Be Edited: In the San Francisco Bay Area, from global corporations to kids, everyone is embracing the breakthrough gene-editing technology CRISPR 
Discover Magazine | Jeff Wheelwright | May 2, 2016

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