News: CMN Weekly (22 October 2021)

Top picks

• Kentucky-based LogicBio Therapeutics has shared early clinical trial results demonstrating the first-ever in vivo genome editing in children using its proprietary GeneRide™ platform. GeneRide™ takes advantage of homologous recombination to enable precise genome editing without the need for nucleases or promoters. The trial, called SUNRISE, is evaluating the safety, tolerability and preliminary efficacy of LB-001, a single-dose genome-editing therapy, in children with methylmalonic acidemia (MMA).
• Intellia Therapeutics announced yesterday that the U.S. FDA had granted orphan drug designation to NTLA-2001 for the treatment of transthyretin (ATTR) amyloidosis. NTLA-2001 is the first CRISPR therapy to be administered systemically to edit a disease-causing gene inside the human body. You can read our previous coverage on NTLA-2001 here.

Industry

• Beam Therapeutics has announced pre-clinical data on its liver-targeting base-editing strategy to correct R83C, one of the primary disease-causing mutations of glycogen storage disease type Ia (GSDIa). The company reported correction of the human gene and restored normal glucose metabolism in a humanised mouse model for GSD1a, without creating double-stranded DNA breaks.
• Cellectis is to present initial pre-clinical data on two novel gene therapies for patients with Severe Combined Immunodeficiency (SCID) and Hyper IgE syndrome at European Society of Gene and Cell Therapy (ESGCT) Congress, which is being held virtually this week. The data will be presented by Toni Cathomen’s team at University of Freiburg, who are collaborating with Cellectis on the therapies, which are developed using Cellectis’ TALEN®-based 'HEAL' genome-editing platform.
• Intellia Therapeutics presents pre-clinical data demonstrating advancements in its broad genome-editing capabilities at ESGCT 2021. Highlights include the first pre-clinical demonstration that Intellia’s allogeneic platform creates immune-evading T cells for future use in cancer treatment, and lipid nanoparticle-based delivery as a more efficient multiplex gene-editing approach.
• Editas Medicine will present data from its ongoing Phase 1/2 BRILLIANCE trial for EDIT-101 in the inherited retinal disorder Leber congenital amaurosis 10 (LCA10) at ESGCT 2021.
• Prime Medicine announces addition of capabilities to prime-editing platform. The latest advances include optimised engineered prime-editing guide RNAs (pegRNA) that were recently shown to improve the efficiency of the editing process several-fold, as well as efficiency improvements through modulation of the DNA mismatch repair pathway.
• Sana Biotechnology Inc.has secured non-exclusive commercial rights to Beam Therapeutics CRISPR-Cas12b nuclease system for certain ex vivo engineered cell therapy programmes. Under the terms of agreement, Sana will pay Beam an upfront payment of $50 million and the license does not include any rights to base editing using Cas12b, which remains at Beam. Sana is a Washington-based biotech company with multiple ex vivo and in vivo cell and gene engineering programmes in oncology, haemoglobinopathies and other genetic diseases.
• A bad month for CRISPR-based therapeutics sends investors packing. Commentary on the recent fall in share prices for three leading CRISPR-based therapeutics companies as investors become uneasy about technology. In this writeup, the falls are attributed mainly to dissapointing clinical readouts from the BRILLIANCE trial (Editas) and the CARBON trial (CRISPR Therapeutics.).

Research

• New research from Princeton University, University of Californa San Francisco, Massachussetts Institute of Technology and Tessera Therapeutics details a novel method called Repair-seq that measures the effects of thousands of genetic perturbations on mutations introduced at targeted DNA lesions, to reveal in exquisite detail how genome editing tools work. The findings were published in Cell earlier his week.
• A team at University of Massachussetts Medical School has explored chemical modifications to double-stranded and single-stranded DNA repair genome-editing templates. They describe several 5′-terminal modifications including the incorporation of triethylene glycol (TEG) moieties, that consistently increased the frequency of precision editing in the germlines of three animal models (Caenorhabditis elegans, zebrafish and mice) and in cultured human cells. The findings were published in eLife this week.

Reviews

• Gene Therapy Approach with an Emphasis on Growth Factors: Theoretical and Clinical Outcomes in Neurodegenerative Diseases. This review focuses on the methods to deliver genetic material to the central nervous system, which includes viral and non-viral vectors and their application in gene therapy.

Huh, heh, wow

• Should we resurrect the woolly mammoth? Harvard bioscience company Colossal is planning to use CRISPR to resurrect the long-time extinct woolly mammoth. This brief piece looks at the scientific approach and movitation behind the proposal.