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CMN Weekly (25 March 2022) - Your Weekly CRISPR Medicine News

Some of the best links we picked up around the internet

By: Karen O'Hanlon Cohrt - Mar. 25, 2022

Top picks

  • In an article published in Gene Therapy this week, scientists from ChristianaCare’s Gene Editing Institute report that CRISPR-induced exon skipping can influence the response to conventional chemotherapy in lung cancer cells. The team, which is developing a new combination cancer therapy using CRISPR to knock out the NRF2 gene to render cancer cells more susceptible to chemotherapy, suggests the need for detailed analysis of DNA sequence alterations following CRISPR-Cas gene editing to evaluate how small precise changes created by guide RNA design and execution could have dramatic effects on phenotypic outcomes.
  • Don't miss our upcoming webinar about CRISPR-based Control of Insect-borne Diseases. The webinar, hosted by CRISPR Medicine News, will feature a presentation by Professor Omar Abkari from University of California, San Diego, about his team's efforts to develop a precise and scalable CRISPR system for mosquito population control. Sign up to this free webinar here.

Research

  • Scientists from AstraZeneca report two strategies to install precise genomic insertions using an SpCas9 nuclease-based prime editor (PEn). The new approach to targeted DNA insertion builds upon prime-editing technology and uses PEn, which combines Cas9 with a reverse transcriptase. They show that this approach can use a range of efficient DNA repair pathways including non-homolgous end joining (NHEJ), which robustly introduces programmed small insertions at DNA double-strand breaks. They also demonstrate that, unlike CRISPR-Cas9, PEn does not induce large unintended deletions at the target site, and this is because PEn efficiently disrupts Cas9 cleavage by destroying its binding site after a successful DNA insertion. The findings were reported in Nature Communications yesterday.
  • CRISPR–Cas systems store fragments of foreign DNA, called spacers, as immunological recordings in so-called CRISPR arrays, which are used to combat future infections. Of the many spacers in an array, the most recent ones are prioritised for immune defence, However, the underlying mechanism remains unclear. Researchers in Germany are now closer to solving this mystery, by showing that the leader region upstream of CRISPR-Cas9 arrays enhances CRISPR RNA (crRNA) processing from the newest spacer, thus prioritising defence against the matching invader. The findings were published in Nature Microbiology earlier this week.
  • In an article published in Nucleic Acids Research earlier this week, researchers in the U.S. show that fusing Escherichia coli DNA polymerase I to Cas9 greatly increases the frequencies of 1-bp deletions and decreases >1-bp deletions or insertions. The approach also greatly decreased the generation of long deletions, including those >2 kb, and templated insertions were increased relative to other insertions. The authors report that counteracting DNA resection was one of the mechanisms perturbing deletion sizes and suggest that their strategy makes it possible to generate refined DNA mutations for improved safety without compromising genome-editing efficiency.
  • Researchers in Greece, Germany and UK report a protocol for the targeted induction of a large chromosomal inversion (>3.7 Mbp) through CRISPR-Cas9-mediated genome editing. As inversions occur at low frequency following Cas9 cleavage, they provide a detailed screening approach of FACS-sorted, single-cell-derived clonal human bronchial epithelial cell (HBEC) cultures. The authors note that although the protocol is tailored to HBECs, it can be readily applied to additional adherent cellular models. The protocol was published recently in STAR protocols.

Industry

Reviews

News from CRISPR Medicine News

  • Monday's interview reported how researchers in South Korea have turned CRISPR-Cas9 as a cancer killer. In a first proof-of-concept study, they confirm the feasibility of using CRISPR-Cas9 to selectively kill cancer cells in various disease models by targeting cancer-specific InDels. Read the interview here.
  • This week's clinical update included news about two gene-editing trials for cancer.Iovance Biotherapeutics' new cancer immunotherapy candidate OV-4001 has been cleared for clinical trial initiation in the U.S. In additional news, the first patient has been dosed in Wugen's WU-CART-007 trial for certain blood cancers. Read the clinical update here.
  • Our sister site CARBON - CRISPR AgroBio News - published another newsletter last Tuesday. Check it out to read about how you can soon indulge in healthier peanuts with less saturated fat. Read the CARBON newsletter here.

To get more of the CRISPR Medicine News delivered to your inbox, sign up to the free weekly CMN Newsletter here.

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News: CMN Weekly (25 March 2022) - Your Weekly CRISPR Medicine News
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