CMN Weekly (6 February 2026) - Your Weekly CRISPR Medicine News

Top picks

• Researchers demonstrated that the ISCro4 bridge RNA-guided recombinase enables programmable genome editing in human cells with deletion and inversion efficiencies exceeding 10% and insertion rates above 6% for multi-kilobase DNA fragments. Using split-bridge RNA guides, the system mediates scarless genomic rearrangements without double-strand breaks or homology-directed repair, achieving proof-of-concept editing at disease-relevant loci including CNBP, CFTR and AAVS1.
• Caribou Biosciences reported updated Phase 1 data for vispa-cel (CB-010), a CRISPR-Cas9-edited allogeneic CAR-T therapy with a PD-1 knockout, showing 86% overall and 63% complete response in second-line or later large B cell lymphoma. Outcomes improved with HLA matching and young donors. The therapy was well tolerated, and a pivotal trial comparing vispa-cel to chemoimmunotherapy is planned. Also see this poster presentation.

Research

• CRISPR-Cas9 editing of EGFR in cervical cancer cells revealed that L14R/Y45M substitutions abolish EGF binding and alter EGFR localisation. Y45M alone reduces binding without affecting localisation. Edited clones showed reduced EGFR expression and phosphorylation, with no off-target mutations but some spontaneous variants. These findings clarify EGFR’s ligand-independent roles and highlight considerations for CRISPR-Cas9-based therapeutic strategies.
• Researchers have developed a dual-fluorescent reporter model using GFP and BFP tagging to discriminate CRISPR-Cas9 editing outcomes at the HBB locus, including in-frame alleles, frameshift indels, large deletions and loss-of-allele events based on fluorescence intensity. The system detects outcome shifts following HDR-enhancing treatments that bulk assays miss, providing a high-throughput platform for evaluating the safety of gene-editing therapies for sickle cell disease.
• Researchers at Profluent Bio have developed Protein2PAM, a deep learning model that predicts and engineers the protospacer-adjacent motif (PAM) specificity of CRISPR-Cas proteins without iterative laboratory screening. Using this approach, they computationally evolved Nme1Cas9 variants with dramatically broadened PAM specificity and up to 50-fold higher cleavage activity than the wild-type enzyme.
• Sequencing of CRISPR RNAs revealed natural abasic modifications at the 5' end – induced by oxidative stress during bacteriophage infection – that suppress off-target cleavages whilst maintaining on-target efficiency in Streptococcus pyogenes Cas9 through limited base pairing or steric constraints. Biologically inspired abasic chemical modifications for guide RNAs improve CRISPR-Cas9 genome-editing specificity, outperforming SpCas9 variants and demonstrating potential for in vivo application.
• A triple-reporter system tracking DSB induction, homology-directed repair and end-joining-mediated targeted insertion revealed that ATR activity is essential for knock-in regardless of donor type, whilst ATM inhibition exhibits donor-dependent effects. With circular plasmid donors, ATM inhibition reduced knock-in and EJ-TI efficiencies, whereas with linear AAV donors, it enhanced knock-in efficiency by suppressing the ATM-p53-caspase 3 apoptotic pathway and partially suppressing classical non-homologous end-joining.

Clinical and preclinical

• YolTech’s in vivo gene-editing therapy YOLT‑203 has received Regenerative Medicine Advanced Therapy (RMAT) designation from the FDA for Primary Hyperoxaluria Type 1. The therapy is designed to knock out HAO1, thereby deactivating glycolate oxidase (GO) and suppressing the synthesis of oxalate precursors. YOLT‑203 aims to provide a one‑time, durable treatment.

Industry

• Fresh off a $257M Series D funding, Cellares and Stanford Medicine are automating manufacturing for gene-edited haematopoietic stem cell therapies using the HARBOR KNOCK CRISPR-Cas method. The platform aims to standardise production and quality control across HIV and over 19 rare monogenic diseases, improving scalability, reproducibility and patient access to durable, potentially curative treatments.
• Sangamo Therapeutics has priced an offering totalling 52.98 million shares and warrants, raising approximately $25 million. Proceeds will support working capital and corporate operations. The offering includes exercise-price adjustments for prior warrants and extended expiration terms.

Screening

• A CRISPR-guided m6A editing screen identified 222 functional methylation sites affecting cancer cell proliferation. In prostate cancer, m6A deposition on CHD9 enhanced its translation via YTHDF1/3, triggered CHD9–MYBBP1A interactions, and activated p21-linked tumour-suppressive pathways. This work maps the functional m6A epitranscriptome and reveals a mechanistic role for CHD9 methylation in growth suppression.
• Using CRISPR-based saturation genome editing, all 342 possible missense mutations in CTNNB1 exon 3 were functionally profiled. The study refined the β-TRCP degron motif and revealed variable β-catenin signalling among mutations. In liver cancer, mutation strength stratified tumour subtypes and correlated with immune infiltration, offering insights into Wnt pathway modulation and informing potential targeted therapies.

Detection

• A CRISPR-Cas12a-based assay integrating RPA and lateral flow strips enables rapid, on-site detection of Listeria monocytogenes in under two hours. Using the hly gene as a target, the method achieved a detection limit of 1.35 CFU/mL in complex foods. Validation against qPCR showed 100% concordance, supporting its potential as a sensitive and practical diagnostic tool.

Meetings and webinars

• A meeting report in Molecular Therapy highlights the ASGCT’s 2025 major advances in in vivo gene editing across multiple organ systems. Key developments included RNA gene writers for correcting HBB in sickle cell disease, in utero base editing via lipid nanoparticles, and AAV-based epigenome editors for neuromuscular and CNS disorders. A recurring theme was urgency: how to rapidly, safely, and equitably deliver these emerging therapies to patients in need.

Reviews

• CRISPR-Cas9-mediated therapeutics: Current clinical trials and therapy approval landscape to treat human diseases. This review outlines the development, clinical translation, regulatory approvals, and future challenges of CRISPR-Cas9 therapeutics, with a focus on sickle cell disease and β-thalassemia, and highlights industry-academia collaboration and the evolving patent and policy landscape.