CMN Weekly (25 October 2024) - Your Weekly CRISPR Medicine News

Top pick

• For the first time, a therapeutic strategy that combines T cell therapy with gene editing will be tested in a clinical trial. The therapeutic candidate in question has been developed under the supervision of Özcan Met PhD, who leads the cell therapy unit at the National Center for Cancer Immune Therapy in Denmark (CCIT-DK). To develop the therapy, T cells are isolated from patients, subjected to CRISPR-mediated knockout of the PD-1 checkpoint protein, and reinfused into patients to boost their ability to fight cancer cells. The trial, which was recently approved by the Danish Medicines Agency, will evaluate the new therapy for the treatment of metastatic melanoma in up to 10 adults with incurable disease. Read the full article (in Danish) here. For English, see our previous interview with Özcan Met shortly after the strategy was first published in Molecular Therapy: Oncolytics. You can hear Özcan Met speaking about this work at next year's CRISPR Medicine Conference (#CRISPRMED25)

Research

• In an article published this week in Journal of Experimental & Clinical Cancer Research, researchers in Italy and Australia report a new strategy to treat the deadly childhood cancer neuroblastoma (NB) based on a combination of CRISPR-mediated gene silencing and a histone deacetylase inhibitor known as entinostat. They found that silencing the endoplasmic reticulum aminopeptidase 1 (ERAP1) gene in combination with entinostat increased the immunogenicity of NB cells, making them responsive to PD-1 therapy. The team observed that while neither strategy alone was effective, a triple combination of ERAP1 silencing + entinostat + PD-1 blockade significantly improved survival rates without toxicity in a mouse model of NB. Read the full article in Journal of Experimental & Clinical Cancer Research here.
• In an article published in ACS Nano this week, researchers in China and US demonstrate that in utero intracerebroventricular (ICV) injection of densely PEGylated lipid nanoparticles (ADP-LNPs) containing an acid-degradable PEG-lipid can safely and effectively deliver mRNA for gene-editing enzymes to the foetal mouse brain, resulting in successful transfection and editing of brain cells. They show that ADP-LNPs containing Cre mRNA could transfect 30% of the foetal brain cells in Ai9 mice without detectable adverse effects on foetal development and post-natal growth. They also report that ADP-LNPs efficiently transfected neural stem and progenitor cells in Ai9 mice with Cre mRNA, which subsequently proliferated and caused over 40% of the cortical neurons and 60% of the hippocampal neurons to be edited in treated mice 10 weeks after birth. Similarly promising findings were also made in a mouse model of Angelman syndrome.
• Researchers in China present a dual amplification CRISPR miRNA assay developed by combining enzyme-free HCR with single-particle analysis. Attomolar detection limits, excellent selectivity, and practicability were achieved by applying this method. They propose that the new assay helps to address challenges associated with current miRNA detection methods that require PCR amplification, including high costs, non-specific amplification, and interference from primer residues in pre-amplification strategies. Their findings were published this week in Chemical Communications.

Industry

• Yesterday, Intellia Therapeutics released new positive results from the ongoing Phase 2 trial of NTLA-2002 in hereditary angioedema (HAE) that further support the therapeutic candidate as a functional cure. The data were published in the New England Journal of Medicine and will be presented this Saturday at the American College of Allergy, Asthma & Immunology meeting. NTLA-2002 is an in vivo CRISPR-editing therapeutic candidate designed to knock out the target gene kallikrein B1 (KLKB1) in hepatocytes. This gene encodes prekallikrein, a precursor of plasma kallikrein, thus its knockout permanently reduces plasma kallikrein activity and halts the production of bradykinin to prevent the painful inflammatory attacks seen in HAE. See the official press release for further details.
• Editas Medicine and Genevant Sciences announced this week that they will collaborate to develop novel mRNA-LNP gene-editing therapeutics. The non-exclusive license agreement will combine Editas' CRISPR Cas12a genome-editing systems with Genevant’s proprietary LNP technology in the development of in vivo gene-editing medicines directed to two undisclosed targets in Editas’ upregulation strategy. See the official press release for further details.
• Poseida Therapeutics is scheduled to present new pre-clinical data that supports non-viral gene editing with its candidate P-KLKB1-101 for the treatment of HAE. P-KLKB1-101 is a liver-directed genetic medicine that uses Poseida's Cas-CLOVER™ site-specific gene-editing system and the new data demonstrate high-fidelity KLKB1 gene editing for the targeted correction of HAE, the ability for controlled dose response, favourable tolerability and liver editing within the predicted therapeutic range. For more details, see the official press release here.
• HuidaGene Therapeutics announced this week that it has appointed TJ Cradick, PhD as Chief Technology Officer to lead the company's delivery science and genome-editing innovations. Dr. Cradick is a pioneer in genome editing and has contributed to notable advances within CRISPR, TALEN, and ZFN technologies. As CSO at Excision BioTherapeutics, he developed the first in vivo CRISPR treatment targeting latent HIV reservoirs. As Head of Genome Editing at CRISPR Therapeutics, he contributed to the approval of the groundbreaking therapy Casgevy^TM, the first-ever approved CRISPR-based treatment. Read more in HuidaGene's press release here.
• AvenCell Therapeutics announced in a press release published this week that it has raised $112 million in a Series B funding round led by Novo Holdings. The company is advancing its proprietary Universal Switchable CAR-T cell therapy platform to develop new treatments for blood cancers and autoimmune diseases. In March of this year, AvenCell reported that the first patient had been dosed in a Phase 1A clinical trial of AVC-201, the company's lead clinical allogeneic cell therapy programme. Read more about that in a previous clinical trial update here.
• Moonwalk Biosciences announced this week that it will present new epigenetic data at ObesityWeek 2024 and The Liver Meeting 2024, both taking place next month. According to a press release, the company will present new data highlighting its epigenetic capabilities in identifying new therapeutic targets for metabolic diseases and liver disorders using its proprietary EpiRead™ and EpiWrite™ platforms.
• Arbor Biotechnologies will highlight new pre-clinical data from its pipeline programmes that support the knock-in applicability of Type V Nucleases at several upcoming/ongoing medical and scientific meetings; American Society of Nephrology (ASN) 2024 Kidney Week Meeting (ongoing), 31^st Annual European Society of Gene and Cell Therapy (ESGCT, ongoing), and ALS One 7^th Annual ALS Research Symposium, November 13-15, Virtual. See the press release for further details.