Your missing links are here (4 December 2020)

Top picks

• Scientists in US successfully use AAV-delivered CRISPR-Cas9 construct to eliminate the simian equivalent to HIV in monkeys. This study gives hopes for a potential cure for HIV, which has proven incredibly difficult to vaccinate against. This piece explains why the new study in monkeys is such a big deal.
• Discussion piece focusing on 5 companies with novel technologies and approaches to gene-editing therapies. Companies discussed include: Spotlight Therapeutics, Tango Therapeutics, Excision BioTherapeutics, Graphite Bio and Precision BioSciences.

Research

• Researchers in the US generate engineer a new Cas9 variant, miCas9, with improved gene-editing efficiency. miCas9 is engineered by fusing a 36 amino acid-long minimal motif to the prototypical spCas9. MiCas9 binds the double stranded DNA (DSB)- repair protein RAD51 through this fusion motif, leading to enrichment of RAD51 at the target locus which conincides with improved DSB-mediated large size gene knock-in and a reduction in off-target indel events.
• A team from Memorial Sloan Kettering Cancer Center (MSKCC) in New York uses CRISPR to dissect the roles of certain genes that promote the growth of tumour cells. The findings point to a potentially new target for aggressive lung adenocarcinoma. Read a summary of the work on MSKCC website here.
• A collaboration between Harvard University, the Broad Institute of MIT and Harvard, and MIT has resulted in in vivo Perturb-Seq, a new technology that can investigate the functions of many different genes in many different cell types simultaneously, within a living organism. The team applied in vivo Perturb-Seq to disrupt 35 genes known to be associated with autism spectrum disorder in mouse embryos, and networks of gene expression observed in neuronal and glial cells suggest new functions for autism-associated genes. The findings were published in the journal Science.
• New findings from Rockefeller University provide the first evidence that telomere shortening, a phenomenom whereby the tips of our chromosomes become shorter throughout life, is good for us. Using CRISPR to recreate several mutations that were seen in certain cancer-prone families, the researchers were able to identify TINF2, a protein that limits telomere length and concomitantly maintains genome stability, thus functioning as a tumour suppressor.

Industry

• California-based biotech Spotlight Therapeutics closes $30 million series A financing round to advance its novel non-viral CRISPR technology. The company is using its proprietary TAGE (Targeted Active Gene Editor) platform to develop modular and programmable CRISPR ribonucleoproteins that are optimised for in vivo delivery for the treatment of blood diseases and cancer.
• Vivlion GmbH (Germany), an innovative gene-editing reagents and screening services company has just signed a worldwide license agreement with Dublin-based ERS Genomics, which will see Vivlion gain access to ERS Genomics CRISPR/Cas9 patent portfolio for the advancement of its gene-editing and screening services. ERS Genomics' CRISPR-Cas9 intellectual property is co-owned by recent Nobel Prize winner and CRISPR pioneer Dr. Emmanuelle Charpentier.
• Gene-editing company Graphite Bio expands leadership team with accomplished pharmaceutical executives to advance programs to the clinic and to achieve continued business growth. Katherine Vega Stultz, who previously held positions at Celgene Corporation joins as Chief Operating Officer and Philip P. Gutry, most recently affiliated with Kronos Bio, joins as Chief Business Officer.
• Leading gene-editing company Intellia Therapeutics announces pricing of public offering of common stock. The gross proceeds from the offering, which was announced on the 1^st December and is expected to close around the 4^th December, are predicted to be in the range of $175 million.

Clinical Trials

• Precision BioSciences reports positive interim Phase 1/2a trial results for its lead allogeneic CAR T-cell therapy candidate, PBCAR0191. PBCAR0191 is under clinical development as an anti-CD19 CRISPR-engineered CAR T-cell therapy for relapsed/refractory Non-Hodgkin Lymphoma (NHL) and R/R B-cell Acute Lymphoblastic Leukemia (B-ALL) and the new results demonstrate safety and encouraging response rates among the 27 patients enrolled.
• Cellectis to share results showing initial safety and anti-leukaemic activity of UCART22 in BALLI-01 Phase 1 study in relapsed or refractory adult B-cell acute lymphoblastic leukemia B-ALL at Annual American Society of Hematology (ASH) meeting this weekend. UCART22 is an CD22 targeting universal CAR T cell therapy developed using TALEN gene-editing technology.
• CRISPR Therapeutics and Vertex Pharmaceuticals announced acceptance to presence clinical data at plenary session of 62nd American Society of Hematology (ASH) Meeting and Exposition this weekend. Data will be presented on behalf of both companies about 7 patients that are currently participating in two ongoing Phase 1/2 clinical trials of the investigational CRISPR/Cas9 gene-editing therapy CTX001 in the severe blood disorders beta-thalassemia and sickle cell disease.

Review

• In Vivo Cancer-Based Functional Genomics. This review article discusses the strengths and shortcomings of various mouse systems and genomic tools including CRISPR-Cas9 that are commonly used for in vivo cancer screens.
• Methodologies and Challenges for CRISPR/Cas9 Mediated Genome Editing of the Mammalian Brain. A comprehensive discussion of the recent advances in genome-editing of whole animals using fertilised eggs and methods for gene editing in specific neuronal populations in the adult or developing mammalian brain. The pros and cons of each approach is also discussed as well as the existing challenges to CRISPR-Cas gene editing in the brain.

Meetings and Webinars

• Warm up to the 62nd American Society of Hematology (ASH) annual meeting that is taking place virtually this weekend (December 5-8, 2020). Clinical data from several leaders in the CRISPR gene-editing field will be presented, including Cellectis, CRISPR Therapeutics and Penn University.
• California-based Allogene Therapeutics announces webinar to review initial ALLO-715 Phase 1 data on December 5, 2020. The company is developing allogeneic CAR T (AlloCAR T™) therapies for cancer and the webinar will specifically include a discussion of results presented at the American Society of Hematology Annual Meeting from the ALLO-715 UNIVERSAL Phase 1 trial in relapsed/refractory multiple myeloma.

Heh, huh wow

• Researchers at Norwegian University of Science and Technology is studying the effects of exercise at the cellular level and sees potential for gene therapies that may mimic the positive cellular effects for those that either cannot exercise or don’t respond well to physical exercise, so-called low-responders. The researchers were recently interviewed here and you can read more about their work in an earlier review article.