CMN Weekly (21 May 2021)

Top picks

• Verve Therapeutics announced a Nature publication earlier this week highlighting the use of its base-editing technology to potently and durably lower blood PCSK9 and LDL-C in cynomolgus monkeys. The proof-of-concept data comes from a pre-clinical study for Verve’s cardiovascular disease programme. Read the company press release here.
• Lab rats are overwhelmingly male, and that's a problem. Sex can influence a cell’s behaviour, and not taking this into account can skew research conclusions.
• Congratulations to Basem Al-Shayeb, PhD student in Jennifer Doudna’s lab at UC Berkeley who made Forbes' "30 Under 30" list of future biotech leaders. We interviewed Basem last year about his role in discovering the highly compact CasΦ system.

Industry

• Metagenomi presented findings on its CRISPR-associated transposases (CAST) system at the American Society of Gene and Cell Therapy (ASGCT) annual meeting last week. CAST allows targetable genomic integration of large DNA fragments, and the company aims to use it to develop new therapies for diseases that are untargetable with current gene-editing tools.
• At the ASGCT meeting last week, Metagenomi also shared data on three new CRISPR-associated gene-editing systems that it had used to perform multiplexed knockout and to integrate a CAR construct into the genome of T cells and natural killer cells.
• Allogene Therapeutics report positive efficacy and safety data from Phase 1 study for ALLO-501 and ALLO-501A in relapsed and refractory Non-Hodgkin lymphoma. The company, which deploys TALEN-based gene editing plans to initiate a Phase 3 study for ALLO-501A later this year.
• Precision BioSciences will present data on its first generation CD19 allogeneic CAR T programme in relapsed and refractory Non-Hodgkin lymphoma at the American Society of Clinical Oncology Meeting next month.

Research

• Researchers at Brown University, US, use CRISPR-Cas9 gene editing to correct a pathogenic mutation in iPSCs derived from a patient with the X-linked neurogenetic disorder Christianson syndrome. The findings were shared on the preprint server BioRxiv.
• A team of researchers in Korea has developed a method called spCas9-assisted true variant labeling sequencing (CARVE-seq), which detects low-frequency mutant alleles with high accuracy. The tool deploys target base-specific cleavage by Cas9 and its accuracy was verified on ten reoccuring single nucleotide variants in human tumours. The findings were published earlier this week.
• Researchers at University of Illinois, US, have developed a new CRISPR controller in which a chemically inducible anti-CRISPR protein AcrIIA4 is engineered to prevent Cas9 from binding to DNA upon the addition of the FDA-approved ligand trimethoprim. The team could show dose-dependant control over CRISPR off-target editing in mammalian cells. The results were published this week.
• Researchers in China have installed CRISPR-Cas12a sensors into a portable glucose meter for point-of-care detection of analytes. In the system, the presence of the target analye induces activation of the collateral cleavage activity of Cas12a. The findings were published in Analyst today.
• A transformer base-editing (tBE) system has been developed that induces efficient editing with only background levels of genome-wide and transcriptome-wide off-target mutations. The new system was developed using a cleavable deoxycytidine deaminase inhibitor (dCDI) domain that is cleaved following binding at target sites. The system was validated following adeno-associated virus (AAV) delivery and PCSK9 targeting in mice. The results are published in Nature Cell Biology.
• Metagenomics analysis from hypersaline environmental samples identified Cas13X and Cas13Y, two compact families of CRISPR-Cas ribonucleases with demonstrated RNA-interfering or RNA-editing activity in mammalian cell lines. The findings, published in Nature Methods earlier this week, suggst the presence of untapped bacterial defense systems in natural microbes that may have potential for RNA-editing applications.

COVID-19

• Mammoth Biosciences’ Vice President of Product Development Tim Patno discusses the potential of CRISPR to revolutionise diagnostics and the challenges involved in scaling up CRISPR-based diagnostics during the COVID-19 pandemic.

Webinars and interviews

• Don't forget the upcoming CRISPR Medicine News webinar on May 26th. Our speakers will discuss the important subject of CRISPR Delivery Systems. Find out more and sign up to attend here.
• Gene Therapy at a Crossroads: The Challenges and Opportunities Ahead. Free on-demand webinar sponsored by Catalent, featuring panelists from Beam Therapeutics and CRISPR Therapeutics. Get access here.
• CRISPR Therapeutics CEO Dr. Samarth Kulkarni joined leaders at the Fifth International Vatican Conference to discuss the promise of CRISPR-based treatments to transform medicine. Watch the recorded interview here.

Review and analysis

• Cutting Through the "Gray Area": An Analysis of the IBC Regulatory Oversight of Applications of CRISPR Technology in Clinical Research. This piece compares CRISPR-developed interventions and existing techniques used to produce biomedical products such as CAR T-cell therapies from a US regulatory perspective.

• Novel therapies in Beta-thalassaemia. This reviews describes the current management strategies for beta-thalassaemia and the novel therapies including gene editing to target ineffective erythropoiesis, improving iron overload and correction of the globin chain imbalance.