CMN Weekly (14 November 2025) - Your Weekly CRISPR Medicine News

Top picks

• Researchers have demonstrated that exposure to low-frequency sound, including Pink Floyd's "Another Brick in the Wall", enhances lipid nanoparticle uptake in neurons and mRNA transfection, achieving a 10-fold increase in gene expression in vitro. In mice administered mRNA-LNPs intravenously, low-frequency sound exposure resulted in increased mRNA expression in the midbrain and thalamus, suggesting a non-invasive method for improving therapeutic delivery to the brain.
• A single intravenous dose of CRISPR Therapeutics' CTX310, an in vivo CRISPR-Cas9 therapy targeting ANGPTL3, safely induced durable, dose-dependent reductions in LDL (up to -87%) and triglycerides (up to -84%) in patients with severe dyslipidaemia. Despite one unrelated death and transient liver enzyme elevations, the Phase 1 trial showed no serious treatment-related adverse events, supporting further development as a one-time lipid-lowering therapy for high-risk cardiovascular patients.

Research

• Conventional CRISPR-CAS9 tools trigger immune responses in host animals, which can systematically distort screening results and mask genuine cancer vulnerabilities. A novel platform called StealTHY circumvents this by using transient Cas9 delivery and autologous reporters, enabling accurate genetic screens in immunocompetent models and revealing the AMH-AMHR2 axis as a therapeutically actionable metastasis pathway.
• In a proof-of-principle study, liver-directed adenine base editing corrected the common ABCC6 c.3490C>T (p.R1164X) variant in a mouse model of pseudoxanthoma elasticum, restoring plasma inorganic pyrophosphate levels and preventing ectopic skin calcification. The approach demonstrates that base editing in hepatocytes could provide a permanent, one-time therapy for this multisystemic calcification disorder.
• Researchers have utilised targeted CRISPR-Cas9 editing, employing homology-independent targeted integration (HITI), to correct the defective 21-hydroxylase gene in a mouse model of congenital adrenal hyperplasia. The approach, delivered via dual recombinant adeno-associated virus, restored enzyme expression, increased corticosteroid production, and reduced adrenal hyperplasia, with effects maintained for up to 15 weeks – beyond the adrenocortical cellular turnover time – providing evidence of successful progenitor cell targeting.
• A new study demonstrates that double-strand break (DSB)-based CRISPR-Cas editing induces megabase-scale loss of heterozygosity (LOH) in ~5% of cells, with the risk amplified by the inhibition of NHEJ and MMEJ pathways. In contrast, Cas9 nickases and adenine base editors did not trigger detectable LOH, underscoring the need for caution with DSB-driven approaches, particularly where genomic stability is critical.
• CRISPR-Cas9 editing in retinal organoids targeting the RHO gene demonstrated delivery and efficiency patterns that closely matched those of in vivo models, despite lower transfection rates compared to HEK293T cells. This validates retinal organoids as predictive, preclinical platforms for refining gene-editing strategies in inherited retinal disorders, such as autosomal dominant Retinitis Pigmentosa.
• Researchers developed CAT-ATAC, a method that adds CRISPR guide RNA capture to the 10× Genomics Multiome assay to simultaneously link perturbation identity, transcriptome, and chromatin accessibility in single cells. Achieving up to 77% capture rates in induced pluripotent stem cells and cancer cell lines, they used the approach to construct gene regulatory networks associated with dasatinib resistance, identifying HIC2 and validating ZFPM2 as contributors to resistance.

Clinical & preclinical

• The FDA reports that it will allow personalised medicines – including CRISPR-Cas and other gene-edited therapies – for rare, fatal diseases to gain approval based on data from a few patients, bypassing traditional trials. Under a new "plausible mechanism" pathway, companies must demonstrate a biological rationale and consistent early clinical benefit, followed by confirmation of efficacy with real-world data. This could expedite personalised gene editing treatments for severe genetic conditions.
• Intellia Therapeutics reported pooled Phase 1/2 data showing that a single 50 mg intravenous dose of lonvo-z, an in vivo CRISPR-Cas9 therapy targeting the KLKB1 gene, achieved deep and durable reductions in plasma kallikrein (mean 89% at month 24) in 32 patients with hereditary angioedema. Notably, 97% of patients were both attack-free and long-term prophylaxis-free as of the data cutoff, with follow-up extending to three years.
• Metagenomi reported preclinical data from its MGX-001 haemophilia A programme, which combines AAV-delivered FVIII gene therapy with lipid nanoparticle-delivered proprietary MG29-1 nuclease for genome editing. In non-human primates, the proposed clinical dose (AAV 5×10¹² vg/kg plus LNP 0.6 mg/kg) achieved average factor VIII activity of 49%, approaching the 50–150% range considered a functional cure, with dose-dependent effects from both components.
• Precision BioSciences' ARCUS-based in vivo gene editor, PBGENE-HBV, showed dose-dependent and durable reductions in HBsAg, as well as direct editing of viral DNA – including cccDNA – in chronic Hepatitis B patients. Liver biopsy confirmed ARCUS-mediated indels, a first in humans. With no dose-limiting toxicities, these Phase 1 results support ARCUS as a viable curative platform targeting the root cause of HBV infection.
• A single dose of Intellia's CRISPR-Cas9 therapy, nexiguran ziclumeran (nex-z), achieved a sustained 87% TTR reduction and stabilised or improved cardiomyopathy markers in ATTR amyloidosis patients over 24 months. Biochemical and functional benefits were observed in most participants, with a reduced mortality rate compared to matched controls. These Phase 1 results support nex-z as a potential one-time treatment for ATTR-CM.

Industry

• Vor Bio priced a $100 million public offering of 10 million shares at $10 each to fund its clinical-stage pipeline, including the CRISPR-Cas-compatible cell therapies under development. The offering supports ongoing Phase 3 trials for telitacicept in autoimmune diseases, aligning with the company's strategy to expand gene-edited treatment platforms.
• BioSpring and metabion have partnered to streamline therapeutic oligonucleotide development, aiming to cut costs and timelines from discovery to commercialisation. By combining nearly 60 years of expertise, they offer integrated high-throughput manufacturing, analytics, regulatory support and companion diagnostics – potentially accelerating CRISPR-Cas and other oligo-based therapies into clinical use more efficiently.
• Precision BioSciences has raised approximately $75 million through a public offering to support the development of in vivo ARCUS gene editing therapies. The deal includes common stock, pre-funded warrants, and five-year warrants, signalling investor confidence in its CRISPR-Cas alternative platform and its therapeutic pipeline for high unmet medical needs.

Third Quarter 2025 Financial Results

• Vor Bio reports Q3 net loss of $813 million and a cash deposit of $171 million.
• Prime Medicine reports Q3 net income of $51 million and a cash deposit of $227 million.
• Iovance Biotherapeutics reports Q3 net loss of $91 million and a cash deposit of $301 million.
• Fate Therapeutics reports Q3 net loss of $32 million and a cash deposit of $41 million.
• Editas Medicine reports Q3 net loss of $25 million and a cash deposit of $166 million.
• CRISPR Therapeutics reports Q3 net loss of $106 million and a cash deposit of $286 million.
• Cellectis reports Q3 with undisclosed net loss and a cash deposit of $225 million.
• Caribou Biosciences reports Q3 net loss of $27 million and a cash deposit of $159 million.
• Modalis Therapeutics reports Q1-Q3 net loss of ¥1,801 million and a cash deposit of ¥3,307 million.
• MaxCyte reports Q3 net loss of $12 million and a cash deposit of $13 million.
• Korro Bio reports Q3 net loss of $18 million and a cash deposit of $102 million.

Reviews

• Research progress of base editing and prime editing tools based on the CRISPR/Cas system. This review summarises the development, characteristics, and applications of CRISPR-based base editors and prime editors, while highlighting current challenges and future directions for improving their precision and efficiency.