CMN Weekly (18 June 2021)

Top picks

• Don’t miss our live CMN webinar on CRISPR Off-Targets on the 23^rd June and hear about CAST-Seq and CRISPECTOR, two of the newest tools for post genome-editing analysis. Sign up to attend the live webinar for free here.
• France-based Eligo Biosciences presented preclinical data on its lead drug candidate, EB003, for the treatment of severe diarrhoea induced by shiga-toxin (Stx) producing E. coli at the Annual CRISPR 2021 meeting last week. This is the first demonstration of gut microbiome modulation and disease control via delivery of CRISPR nuclease.
• For those of you following the CRISPR patent saga, here is the latest update.

Industry

• Massachusets-headquartered gene-editing and gene therapy company Hunterian Medicine LLC has been awarded a Therapeutics Development Award by the Cystic Fibrosis Foundation. The award, through the Foundation’s Path to a Cure initiative that seeks to replace, restore or repair cystic fibrosis transmembrane conductance regulator (CFTR) genes, will support Hunterian’s efforts in advancing its AAV and CRISPR-gene editing platform technology to develop a gene therapy for cystic fibrosis.
• CRISPR Therapeutics and California-based Capsida Biotherapeutics, which recently emerged from stealth mode, announce a strategic collaboration to research and develop CRISPR-Cas9 in vivo gene editing therapies for the treatment of familial amyotrophic lateral sclerosis (ALS) and Friedreich’s ataxia (FA). The new therapies will be delivered using highly specific adeno-associated virus (AAV) vectors generated using Capsida’s high-throughput AAV engineering platform.
• Following recent communication from the FDA about its considerations around cutting nicotine in cigarettes, Demeetra AgBioannounces that it can produce harm-reduced tobacco products through genome-editing. Read about Demeetra's technology and future plans in our interview with CEO Jack Crawford published this week.
• Intellia Therapeutics will present interim clinical data from its ongoing Phase 1 Study of NTLA-2001 for the treatment of transthyretin (ATTR) amyloidosis at the 2021 Peripheral Nerve Society Annual Meeting on the 26^th June 2021. NTLA-2001 is a CRISPR-Cas9 in vivo genome-editing therapy designed as a single-dose treatment for long-term disease control.
• Allogene Therapeutics recently presented positive Phase 1 data on its two anti-CD19 gene-edited CAR T-cell candidates anti-ALLO-501 and ALLO-501A. The new therapies are being developed for relapsed or refractory Non-hodgkin lymphoma and the data was presented in poster format at the 2021 Annual Meeting of the American Society of Clinical Oncology.
• Precision BioSciences has reported updated Phase 1/2a interim data on strategies designed to optimise the durability of allogeneic CAR T therapy in relapsed or refractory Non-hodgkin lymphoma. The promising data concerns 12 heavily pre-treated patients who received PBCAR0191 CAR T cells following enhanced lymphodepletion, and reveals that enhanced lymphodepletion may be a strategy to help suppress host immune rejection.
• Gene-editing company ToolGen and 3D bioprinting company T&R Biofab, both in South Korea, have signed a joint research deal to develop induced pluripotent stem cell (iPSC) therapies that can overcome immune rejection. The partners will use CRISPR to edit genes that mediate immune rejection in order to develop allogeneic cell transplantation products for a range of regenerative indications.

Research

• A team from Norway, Sweden and Finland has studied the effect of 450 DNA repair protein-Cas9 fusions on CRISPR genome-editing outcomes. They found that most fusions only improve precision genome editing modestly. Cas9 fused to DNA polymerase delta subunit 3 (POLD3) enhanced editing by accelerating the initiation of DNA repair. The team concludes that while fusions can improve homologous recombination-driven CRISPR outcomes, most fusions require locus- and cell-type specific optimisation. The findings were shared this week on the preprint server bioRxiv.
• Researchers in Germany have developed a reporter system to enrich for scarce CRISPR-Cas9 knockout cells in technically challenging settings such as patient-derived cellular disease models. The new system involves cloning the gene of interest upstream of an out-of-frame fluorochrome that is expressed only upon successful gene editing. The findings were published in Science Reports this week.
• New research led by Matthew Porteus at Stanford University demonstrates the preclinical feasibility of HBB gene correction in haematopoeitic stem and progenitor cells (HSPCs) from healthy and sickle cell disease patient donors. The team achieved up to 60% HBB allelic correction at clinical-scale cell manufacturing levels. Transplant into immunodeficient mice resulted in 20% gene correction with multilineage engraftment with a promising long-term safety profile. The same team recently demonstrated correction of the related disease beta thalassemia using CRISPR-Cas9 editing.
• A team in China has used high-throughput primer-extension-mediated sequencing approach to analyse the editing efficiency, specificity and protospacer adjacent motif (PAM) compatibility of a panel of SpCas9 variants at multiple target sites in depth, and their findings validate the high fidelity or broad-editing range reported for these variants. They also find that existing Cas9 variants cannot effectively suppress genome instability elicited by CRISPR-Cas9 editing, and raise this as an urgent issue. The findings were published in Nucleic Acids Research this week.
• CRISPRloci has been developed as a new server that provides the first resource for the prediction and assessment of all possible CRISPR loci. The server is built using machine learning and constitutes a full suite for CRISPR-Cas system characterisation that offers annotation quality previously available only after manual inspection. The findings were published in Nucleic Acids Research this week.
• Sherlock Bioscience's SHERLOCK Cas13a-based detection platform has been used to develop a novel CRISPR-based malaria diagnostic that can detect and discriminate all Plasmodium species known to cause human malaria, as well as genotype for drug resistance. The findings were published in EBioMedicine this week.

COVID-19

• The 221b Foundation, a nonprofit organisation established by Sherlock Biosciences, has granted a licence to ALBOT Technologies, USA and India, to develop, manufacture and distribute Sherlock’s CRISPR COVID-19 diagnostic kits in India.
• Scientists from University of California-Irvine have developed RNA-Encoded Viral Nucleic Acid Analyte Reporter (REVEALR), a highly sensitive multicomponent XNA-based nucleic acid detection platform that combines analyte preamplification with X10-23-mediated catalysis to detect SARS-CoV-2. The findings were published in Journal of the American Chemical Society.

Review and analysis

• Nonviral genome engineering of natural killer cells. This review focuses on current non-viral methods of gene transfer for the improvement of cancer immunotherapy using engineered natural killer (NK) cells.

Regulatory

• Citizens’ jury commences in Canberra: A University of Canberra partnership will host two dozen ordinary Australian citizens this week, to debate whether or not human genome editing should be permitted.

Conferences and webinars

• CRISPR: New Techniques and Complex Models. A virtual half-day event on the 30th June with speakers from industry, adacemia and clinical backgrounds. More details and sign-up information here.

Heh, huh wow

• Scientists Used CRISPR to Engineer a New ‘Superbug’ That’s Invincible to All Viruses. Researchers at University of Cambridge used CRISPR to replace over 18,000 codons with synthetic amino acids that don’t exist anywhere in the natural world, making a bacteria that is virtually resistant to all phages. Findings published recently in Science.