CMN Weekly (14 July 2023) - Your Weekly CRISPR Medicine News

Some of the best links we picked up around the internet

By: Karen O'Hanlon Cohrt - Jul. 14, 2023
News

#CRISPRMED24

Top picks

  • In an article published in Nature Biomedical Engineering this week, a team of researchers at Yale University unveil MAJESTIC, a brand new gene delivery system based on Sleeping Beauty (SB) transposase delivered by an adeno-associated virus, which encodes an SB transposon that includes the desired transgene. The new technology allows CRISPR-independent, DNA-free and non-lentiviral gene delivery into diverse human cell types with high efficiency and cell viability. MAJESTIC technology has been exclusively licensed to Cellinfinity Bio, which according to a press release, plans to use it to develop novel therapies for a broad range of diseases.

Research

  • In an article published earlier this week in ACS Central Science, scientists at Verve Therapeutics report a high-fidelity, top-down mass spectrometry workflow to provide direct and quantitative assessments of highly modified gRNAs. The aim of the work was to advance gRNA characterisation to ensure that the spacer region of any gRNA is of high fidelity, since it is this which dictates the on-target editing site as well as potential undesired off-target edits.
  • Mutations in the Crumbs-homologue-1 (CRB1) gene lead to a spectrum of severe inherited retinal diseases, including retinitis pigmentosa (RP). Establishing genotype-phenotype correlations in CRB1 patients is inherently difficult because of the variability and phenotypic overlap between CRB1-associated diseases. To address this challenge, researchers at various institutes in the U.S. leveraged the potential of induced pluripotent stem cell (iPSC)-derived patient retinal organoids to model CRB1 RP patient phenotypes, and developed a correction strategy for the most prevalent CRB1 mutation (Gly827Val) using CRISPR-Cas9-mediated homology-directed repair. The findings were published in Advances in Experimental Medicine and Biology. In a separate article in the same journal, the authors also report the results of an analysis of the Leiden Open Variation Database to identify CRB1 pathogenic variants correctable with CRISPR base- and prime editing. You can read findings from that study here.
  • Earlier this week, scientists in China reported a new small adenine base editor (sABE) with significantly reduced size compared to existing ABEs. The new sABE was generated by subjecting ABE8e to large single deletions in the REC2 and HNH domains of SpCas9, and stacking these deletions to create sABE. The team found that sABE showed higher precision than the original ABE8e, with proximally shifted protospacer adjacent motif (PAM) editing windows (A3- A15), and comparable editing efficiencies to 8e-SaCas9-KKH. The sABE system efficiently generated A-G mutations at disease-relevant loci in human cell lines, and was successfully used to edit the genome of mouse embryos by microinjecting sABE mRNA and sgRNA into zygotes. The findings were published in BMC Biology.
  • A team of researchers at Columbia University (U.S.) have added to the prime-editing toolbox, with the development of a new prime editor based on the avian myeloblastosis virus (AMV)-RT, and demonstrated its applicability for the installation of the PRPH2 c.828+1G>A mutation (associated with retinal diseases) in HEK293 cells. Their findings were published today in Advances in Experimental Medicine and Biology.

Industry & clinical

  • Caribou Biosciences reported positive clinical data yesterday, from the dose escalation phase of the ongoing CB-010 ANTLER Phase 1 trial in relapsed or refractory B-cell non-Hodgkin lymphoma B-NHL. Amongst the findings, Caribou announced that CB-010 exhibited a 94% overall response rate and 69% complete response (CR) rate, and 44% CR rate at ≥6 months following a single dose of CB-010. CB-010 is Caribou’s most advanced cell therapy candidate and is derived from healthy donor T cells that are edited using the company's proprietary Cas9 chRDNA technology. CB-010 was the first allogeneic CAR-T cell therapy with a CRISPR-mediated PD-1 deletion to be cleared for a clinical trial. You can read more about CB-010 and previous clinical data in a recent clinical trial update here.
  • Caribou Biosciences announced yesterday that it has commenced an underwritten public offering of $100 million of shares of its common stock. See press release here for more details.

Reviews

Patent news

Huh, heh, wow

  • Building a Better Forest Tree With CRISPR Gene Editing. In an article published yesterday in Science, researchers at North Carolina State University report using multiplex CRISPR editing to breed poplar trees with reduced levels of lignin, the major barrier to sustainable production of wood fibers, while improving their wood properties. The findings reveal the potential to make fiber production a greener, cheaper, and more efficient process, for everything from paper to diapers.

News from CRISPR Medicine News

  • In a recent proof-of-concept study, researchers at SNIPR Biome and collaborators confirmed the feasibility of using CRISPR-armed phages to selectively target clinically-relevant E. coli strains. Their findings highlight new possibilities in using phage therapy to address the challenges of antibiotic treatments and antibiotic-resistant bacteria. Read more in our latest interview with SNIPR Biome scientists Y. Emre Gencay, Eric van der Helm, and Milan Zdravkovic here.

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News: CMN Weekly (14 July 2023) - Your Weekly CRISPR Medicine News
News: CMN Weekly (14 July 2023) - Your Weekly CRISPR Medicine News
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