CRISPR Weekly Roundup: Advancements in Gene Editing and Clinical Trials
核心洞察
Beam Therapeutics reported a patient death in their BEAM-101 sickle cell disease (搜索) trial, likely due to the conditioning regimen.
AstraZeneca scientists engineered PsCas9 (搜索) for therapeutic genome editing in mouse liver, showing promise for hypercholesterolemia (搜索) treatment.
YolTech Therapeutics (搜索)' novel LNP system delivers base editor mRNA to bone marrow cells, activating foetal haemoglobin production for blood disorder treatment.
Beam Therapeutics has announced the death of a patient participating in the Phase 1/2 trial evaluating BEAM-101, a base-editing therapy candidate for sickle cell disease (搜索) (SCD). The company indicated that the death, resulting from respiratory failure four months post-infusion, was likely linked to the pre-conditioning regimen rather than the BEAM-101 treatment itself.
Advancements in CRISPR Technology
AstraZeneca, in collaboration with the University of Texas and LIVESTRONG Cancer Institutes, has reported advancements in engineered PsCas9 (搜索). This Type II-B family enzyme, previously shown to edit the mouse liver genome without detectable off-target effects, has now been successfully delivered via lipid nanoparticles (LNPs) for therapeutic genome editing in mouse liver. The team engineered PsCas9 for increased activity while maintaining precision and safety. A single dose of mRNA encoding ePsCas9 and its gRNA, formulated with LNPs, resulted in high levels of editing in the Pcsk9 gene, a clinically relevant target for hypercholesterolemia (搜索) treatment. These findings were published in Nature Communications.
Novel Delivery Systems for Blood Disorders
YolTech Therapeutics (搜索), in collaboration with East China Normal University, has published a study demonstrating a novel LNP system for delivering base editor mRNA directly to bone marrow cells and haematopoietic stem cells. A single or repeated intravenous injection of this system effectively edited essential genes and significantly activated foetal haemoglobin production, showing therapeutic potential for treating monogenic blood disorders such as β-thalassemia (搜索) and sickle cell disease (搜索). The study is available on BioRxiv as a preprint.
Allogene Therapeutics' ALLO-316 Shows Promise in Renal Cell Carcinoma
Allogene Therapeutics shared positive Phase 1 data for ALLO-316 in heavily pre-treated patients with advanced renal cell carcinoma (搜索). ALLO-316, an allogeneic TALEN-edited cell therapy candidate, yielded an overall response rate of 50% in the TRAVERSE trial. The data highlight the ability of Allogene's CD70 Dagger® Technology to promote robust expansion and persistence of ALLO-316 with standard lymphodepletion.
Caszyme and Integra Therapeutics Collaborate on Gene Therapy
Caszyme (搜索) and Integra Therapeutics (搜索) have entered into a licensing agreement to develop safer and more efficient gene and cell therapies. Integra Therapeutics will incorporate Caszyme’s novel Cas12l nucleases into its FiCAT 2.0 gene-writing platform, following successful in vivo and ex vivo studies. Caszyme will receive milestone payments up to 40 million euros in addition to royalties on sales.
Other Industry Updates
Several companies have provided third-quarter updates, including Poseida Therapeutics, Iovance Therapeutics (搜索), Allogene Therapeutics, Caribou Biosciences, Editas Medicine, Vertex Pharmaceuticals, Cellectis, Intellia Therapeutics, ProQR Therapeutics, CRISPR Therapeutics, 2seventybio (搜索), and Verve Therapeutics. These updates cover financial results, clinical trial progress, and pipeline development in various therapeutic areas.