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Journal Club July 31st 13:00 EDT / 18:00 UK

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The July edition of the Journal Club has us taking a look at a recent paper that casts doubt and concern over the use of CRISPR Cas9 for gene editing. The researchers raise concerns that using it may result in genomic damage, something that was missed by previous researchers working with the powerful gene editing tool.

CRISPR–Cas9 is poised to become the gene editing tool of choice in clinical contexts. Thus far, exploration of Cas9-induced genetic alterations has been limited to the immediate vicinity of the target site and distal off-target sequences, leading to the conclusion that CRISPR–Cas9 was reasonably specific. Here we report significant on-target mutagenesis, such as large deletions and more complex genomic rearrangements at the targeted sites in mouse embryonic stem cells, mouse hematopoietic progenitors and a human differentiated cell line. Using long-read sequencing and long-range PCR genotyping, we show that DNA breaks introduced by single-guide RNA/Cas9 frequently resolved into deletions extending over many kilobases. Furthermore, lesions distal to the cut site and crossover events were identified. The observed genomic damage in mitotically active cells caused by CRISPR–Cas9 editing may have pathogenic consequences.

Kosicki, M., Tomberg, K., & Bradley, A. (2018). Repair of double-strand breaks induced by CRISPR–Cas9 leads to large deletions and complex rearrangements. Nature Biotechnology.

About the author
Oliver Medvedik

Oliver Medvedik

Oliver Medvedik, Co-founder of Genspace citizen science laboratory in Brooklyn NY, earned his Ph.D. at Harvard Medical School in the Biomedical and Biological Sciences program. As part of his doctoral work he has used single-celled budding yeast as a model system to map the genetic pathways that underlie the processes of aging in more complex organisms, such as humans. Prior to arriving in Boston for his doctoral studies, he has lived most of his life in New York City. He obtained his bachelor’s degree in biology from Hunter College, City University of New York. Since graduating from Harvard, he has worked as a biotechnology consultant, taught molecular biology to numerous undergraduates at Harvard University and mentored two of Harvard’s teams for the international genetically engineered machines competition (IGEM) held annually at M.I.T. Oliver is also the Director of The Maurice Kanbar Center for Biomedical Engineering at the Cooper Union, New York City. The Maurice Kanbar Center for Biomedical Engineering is open to all Cooper Union faculty and students working on bioengineering projects requiring equipment and space for tissue culture, genetic engineering, biomechanics, and related research. Faculty that is currently using the facility are pursuing groundbreaking biomedical research in such fields as biomedical devices, tissue engineering, obstructive sleep apnea biomechanics also collaborating with several major New York City-based hospitals. The Kanbar Center continues to provide space for undergraduate teams participating in the international genetically engineered competition (iGEM) during the summer, as well as space for courses that offer a biological laboratory component.
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