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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, 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.
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