CMN Weekly (2 December 2022) - Your Weekly CRISPR Medicine News

Top picks

• A team of scientists led by Stephanie Cherqui PhD at the Department of Pediatrics at University of California, San Diego School of Medicine, has been awarded $4.8 million by the California Institute for Regenerative Medicine (CIRM) to advance a CRISPR-Cas9 based approach to cure Friedreich’s ataxia (FA), an inherited, degenerative neuromuscular disorder. The approach, which is aimed to result in a one-time lifelong treatment for FA, builds upon previous work by the team, which demonstrated that CRISPR-Cas9 could be used to edit the genomes of haematopoietic stem cells isolated from patients with FA. Read more here.
• After three years in prison, ‘CRISPR babies’ scientist is attempting a comeback. This piece in STAT looks at the latest news surrounding Jiankui He, the Chinese biophysicist who has recently been released from prison having served time for his central role in the so-called CRISPR babies scandal.

Research

• A team of researchers at Cornell University, U.S., reports in Nature this week that they have reconstituted the approximately 1 MDa type V-K CRISPR-associated transposon (CAST) transpososome from Scytonema hofmannii (ShCAST) and determined its structure to near-atomic resolution (3.5 Å) using single particle cryo-electron microscopy (EM). CRISPR-associated transposons (CASTs) are programmable mobile genetic elements that insert large DNA cargo using an RNA-guided mechanism, and the findings from this study suggest potential avenues for improving CAST transposition for precision genome-editing applications.
• In an article published recently in Science Advances, a team based in the U.S. and Russia share findings that help to explain the mechanism of prespacer generation. Prespacers are ~33-bp double-stranded DNA fragments with a ~4-nt 3′ overhang that play a role in primed adaptation, a process whereby DNA targets complementary to spacers get degraded and serve as a source of new spacers. The main findings include that RecJ is the main exonuclease trimming 5′ ends of prespacer precursors, although its activity can be partially substituted by ExoVII, and that the RecBCD complex allows single strand–specific RecJ to process double-stranded regions flanking prespacers.
• Scientists in China report engineering of efficiency-enhanced Cas9 and base editors with improved gene therapy efficacies. The team found that fusing a high mobility group domain (HMG-D) to the N-terminus of SpCas9 (named efficiency-enhanced Cas9, eeCas9) significantly increased editing efficiency by 1.4-fold on average, and that the HMG-D domain also enhanced the activities of non-NGG PAM Cas9 variants, high-fidelity Cas9 variants, smaller Cas9 orthologs, Cas9-based epigenetic regulators, and base editors in cell lines. The full findings were published in Molecular Therapy this week.
• A team in China report spatiotemporal and efficient control of CRISPR-Cas9- and Cas12a-mediated genome editing using conformational restricted gRNAs. Their approach relied on only two or three pre-installed photo-labile substituents followed by an intramolecular cyclisation, which the authors suggest represents a robust synthetic method in comparison to the heavily modified linear gRNAs that often required extensive screening and time-consuming optimisation. The strategy was applied to direct the precise cleavage of GFP and VEGFA within a pre-defined cutting region without notable editing leakage in live cells, and light-mediated gene editing was also acheived in embryos. The full findings were published yesterday in Angewandte Chemie.

Industry

• Caribou Biosciences announced in a press release published earlier this week that the FDA has granted Regenerative Medicine Advanced Therapy (RMAT) and Fast Track Designations to CB-010 for the treatment of relapsed or refractory large B cell lymphoma and non-Hodgkin lymphoma, respectively. CB-010 is an allogeneic anti-CD19 CAR-T cell therapy, which is derived from healthy donor T cells that are genome-edited using the company's next-generation CRISPR-Cas technology based on CRISPR hybrid RNA-DNA (chRDNAs). Read more about CB-010 in our previous clinical update here.
• Allogene Therapeutics' R&D showcase held earlier this week featured haematologic and solid tumour advances across the company's AlloCAR T™ platform. Clinical updates on the company’s haematologic programmes focused on investigational products targeting CD19 and BCMA for the treatment of large B cell lymphoma and multiple myeloma, respectively. The solid tumour presentation provided the first look at initial clinical data on ALLO-316, an AlloCAR T product candidate targeting CD70 for the treatment of clear cell renal cell carcinoma. Read more in the company's press release here.
• Intellia Therapeutics announced pricing of public offering of 6,550,219 shares of common stock earlier this week, at a public offering price of $45.80 per share. Goldman Sachs & Co. LLC is the sole underwriter for the offering, which is expected to close on or about December 2, 2022, subject to customary closing conditions.
• ERS Genomics announced that it has licensed its CRISPR-Cas9 intellectual property to Cosmo Bio, Japan. Cosmo Bio’s mission is to provide the latest information on technological advancements and products from trusted manufacturers for establishments involved in biology, such as educational organizations, research institutions, and inspection agencies worldwide.
• Sherlock Biosciences announced this week that it has secured funding to further develop its CRISPR-based, instrument-free molecular diagnostic testing platform. Sherlock is expected to use the funding to improve the specificity and sensitivity of its testing platform, which allows for the multiplexed detection of multiple infectious diseases from a single patient sample. Read more about Sherlock's vision for CRISPR-based diagnostics in our interview with CEO Brian DeChairo here.

Detection

• A team in China has developed a novel and efficient strategy using the CRISPR-Tag system to detect herpes simplex virus 1 (HSV-1) DNA in host cells. The two-color imaging system based on CRISPR-Cas9 technology can quantitatively detect HSV-1 genomes in living cells, by using a recombinant HSV-1 harboring an ~600-bp CRISPR-Tag sequence which can be sufficiently recognised by dCas9-fluorescent protein (FP) fusion proteins. The full findings were published yesterday in Journal of Virology.

Reviews

• CRISPR-Cas9: Taming protozoan parasites with bacterial scissor. This review article looks at the CRISPR-based approaches explored to date to better understand the biology of protozoan parasites, as well as how CRISPR and related technologies may aid in the development of novel anti-protozoan strategies in future.
• CRISPR/Cas9: a tool to eradicate HIV-1. This review summarises recent advances based on CRISPR to target the proviral HIV-1 genome, as well as associated challenges and future prospects.
• Enabling Precision Medicine with CRISPR-Cas Genome Editing Technology: A Translational Perspective. This piece highlights the challenges and opportunities offered by the CRISPR-Cas toolbox together with delivery vehicles, to realise its use for therapeutic gene editing. The authors also summarise current clinical progress and discuss the obstacles the CRISPR-Cas system faces for successful clinical translation.
• Gene Editing and Human iPSCs in Cardiovascular and Metabolic Diseases. This piece focuses on induced pluripotent stem cells (iPSCs) and CRISPR-Cas9 in the study and cure of cardiovascular and metabolic diseases. The authors summarise the state-of-the-art knowledge about the possibility of editing iPSC genomes for therapeutic applications without compromising their pluripotency and differentiation, using CRISPR-Cas technology, in the field of cardiovascular and metabolic diseases.

News from CRISPR Medicine News

• For this week's feature article, we spoke with Samantha Maragh from the US National Institute of Standards and Technology (NIST). Samantha discusses the significance of the recent publication of a set of standardised genome-editing terms in a community-based project spearheaded by NIST. Read the interview here.

Huh, Heh, Wow

• The scientific breakthrough that promises to end egg shortages. According to this article in the UK Telegraph, scientists are close to publishing new research on the creation of an avian flu-resistant chicken using CRISPR.