CMN Weekly (13 February 2026) - Your Weekly CRISPR Medicine News

Top picks

• A novel CRISPR-based mitochondrial gene editing tool, RMTS-CRISPR, overcomes the challenge of delivering guide RNAs into mitochondria by fusing a 30 nt targeting sequence derived from a mitochondrion-localised long non-coding RNA to sgRNA. The system achieved heteroplasmic mtDNA shifting efficiencies of up to 26.37% in m.3243A>G mutant cell models and 26.79% in vivo, offering a promising approach for correcting heterogeneous mitochondrial DNA mutations.
• A Cas13d RNA-targeting therapy selectively eliminates uveal melanoma cells by degrading RasGRP3 mRNA, an essential but undruggable transcript. Delivered via lipid nanoparticles, the system exploits both targeted knockdown and collateral RNA cleavage, killing over 97% of tumour cells while sparing healthy tissue. This non-genome-editing CRISPR strategy offers a potent, selective approach for otherwise untreatable cancers.

Research

• Researchers advanced their CRISPR-based Pro-Active Genetics (Pro-AG) system by integrating it into a conjugative transfer platform, enabling efficient spread of anti-antibiotic-resistance cassettes between bacterial strains. They also characterised a complementary homology-based deletion mechanism that precisely removes target DNA sequences and serves as a built-in safeguard against uncontrolled cassette dissemination – expanding Pro-AG's potential for microbiome engineering and clinical interventions against antibiotic resistance.
• The OREC platform integrates light- and drug-responsive control of dCpf1-based CRISPR regulators to enable precise, reversible, and multiplex gene modulation. In osteoporotic fracture models, OREC simultaneously activated Bmp2 and repressed Dkk1, enhancing bone repair. This chemogenetic–optogenetic system advances CRISPR-based therapies by achieving coordinated, spatiotemporal control of multiple endogenous genes in complex tissues.
• Using dHyperLbCas12a with RNA Pol II-driven crRNA arrays, researchers achieve highly multiplexed CRISPR-based modulation of cis-regulatory elements. The system enables simultaneous activation and repression in diverse cell types, including primary immune and stem cells. It allows dissection of combinatorial CRE interactions, advancing the study of gene regulation through scalable, programmable expression control.
• A Cas13d RNA-targeting therapy selectively eliminates uveal melanoma cells by degrading RasGRP3 mRNA, an essential but undruggable transcript. Delivered via lipid nanoparticles, the system exploits both targeted knockdown and collateral RNA cleavage, killing over 97% of tumour cells while sparing healthy tissue. This non-genome-editing CRISPR strategy offers a potent, selective approach for otherwise untreatable cancers.
• DAMAGE (Death Manipulation Gene) integrates gasdermins within the type III-E CRISPR framework to trigger pyroptosis upon recognition of specific target RNAs. The system selectively identifies and eliminates virus-infected, cancerous, and senescent cells based on their altered RNA transcriptomes, with additional promise as an mRNA-LNP therapeutic platform, offering a programmable approach to controlled cell death induction in RNA-heterogeneous diseases.
• Multiplexed in vivo CRISPR-Cas9 editing of the ten most frequently mutated tumour suppressor genes in the mouse endometrium generated serous endometrial intraepithelial carcinomas and uterine carcinosarcomas that faithfully recapitulate the histological, molecular and genomic features of human high-risk endometrial carcinoma. The model captured clonal heterogeneity, chromosomal instability and oncogenic mutations in histologically normal tissue – providing a versatile platform for studying tumour evolution in aggressive gynaecological cancers.
• A UK and Korean study has developed a machine learning pipeline that integrates single-cell RNA sequencing with CRISPR screens and protein network analysis to identify novel drug targets for kidney cancer. The work prioritised repurposable, FDA-approved drugs that act on tumour-intrinsic vulnerabilities, demonstrating superior efficacy compared with existing therapies in preclinical models.
• CRISPR–PAMdb aggregates PAM profiles for 8003 Cas9 orthologs from microbial genomes, while the CICERO model predicts PAM preferences directly from protein sequence using deep learning. CICERO extends predictions to over 50,000 additional Cas9s, including 17,453 with high confidence. This integrated resource expands PAM diversity exploration, enabling broader target-site selection for genome-editing applications.
• Researchers present a systematic framework for designing and executing CRISPR-Cas9 knockout experiments that maximise functional gene disruption while minimising off-target effects. By coupling optimised sgRNA selection with experimental validation, they show that frameshift-inducing indels effectively trigger nonsense-mediated decay, generating null alleles. The protocol delivers reproducible, interpretable phenotypes, providing a robust standard for loss-of-function studies in diverse cellular contexts.

Clinical and preclinical

• Precision BioSciences’ PBGENE-DMD, an in vivo gene editing therapy using ARCUS for Duchenne muscular dystrophy, has received FDA clearance to begin clinical trials. The approach excises mutations in exons 45–55 of the dystrophin gene, aiming to restore near full-length dystrophin protein (~80%), surpassing current micro-dystrophin therapies. This first-in-class strategy targets the largest genetic subset of DMD patients.

Q4 and full-year 2025 financial results

• Vertex Pharmaceuticals reports full-year net income of $4.0 billion and a cash deposit of $12.3 billion. Q4 net income was $1.2 billion.
• CRISPR Therapeutics reports full-year net loss of $582 million and a cash deposit of $2.0 billion. Q4 net loss was $131 million.

Delivery

• A novel class of Coomassie brilliant blue-derived lipidoids was developed to deliver adenine base editor ribonucleoproteins to the retina, achieving a 120-fold increase in base editing compared to RNP alone. Subretinal injection of liposome-CBB11-RNP complexes restored scotopic ERG b-wave responses in the rd12 mouse model of inherited retinal disease – demonstrating the potential of CBB-augmented delivery systems for single-dose CRISPR-based precision medicines in the eye.
• Using DNA origami-CRISPR complexes, researchers demonstrated nucleolin-targeted genome editing in cervical cancer cells, coupling GFP-based diagnostics with therapeutic E7 oncogene disruption. The complexes were assembled from long single-stranded DNA produced via Ouroborosyn-ssDNA, a new enzymatic replication platform that combines phi29 DNA polymerase with machine-learning-guided optimisation to synthesise strands up to 15,000 nt with enhanced yield and purity – establishing a scalable pathway for precision nanomedicine applications.
• Engineered Phage Inducible Chromosomal Islands (ePICIs) delivering CRISPR-Cas9 modules targeting small RNA genes demonstrated bactericidal activity against Staphylococcus aureus without chromosomal integration. Despite Bap-mediated biofilm protection in vitro, ePICIs achieved efficacy comparable to vancomycin in a mouse mastitis model – highlighting that antibiofilm therapies should not be dismissed based solely on in vitro performance and positioning non-replicative ePICIs as a promising alternative for treating localised infections.

Screening

• Researchers constructed a library of over 300 full-length chromatin regulators from humans, plants, yeast, protozoa and viruses, fusing each to DNA-binding domains to test their effects on transcriptional repression and activation. Using pooled CRISPR screens, they identified cross-kingdom regulators that outperform existing tools for programmable gene expression control – including RCOR1 and MTA2, which function as universal eukaryotic repressors across plants, yeast, and human cells.
• Using high-throughput CRISPR-Cas9 screening in Xenopus, researchers functionally validated candidate genes identified from whole-exome sequencing of patients with congenital heart disease, including Filamin B (FLNB), a novel gene linked to heterotaxy and cardiac defects. Disrupting flnb reproduced key features of the human phenotype, including impaired motile cilia function, while rescue experiments confirmed functional conservation – directly implicating actin cytoskeletal disruption in ciliogenesis and left–right patterning defects.
• A genome-wide CRISPR-Cas9 knockout screen, combined with stiffness-based microfluidic sorting, identified over 700 genes that regulate cell mechanics in ovarian cancer. Notably, loss of PIK3R4, CCDC88A, and GSK3B markedly increased stiffness and correlated with poorer patient survival. This study establishes a scalable platform linking genotype to mechanotype, with the potential to uncover mechanical biomarkers and therapeutic targets in metastatic cancer.
• A CRISPR-based epitranscriptomic screen identified 222 functional m6A sites regulating cancer cell proliferation, many in a cell-specific manner. An m6A site in CHD9 acted as a potent tumour suppressor in prostate cancer by enhancing translation via YTHDF1/3, promoting CHD9–MYBBP1A interaction, and activating CDKN1A. This study maps functional m6A sites at scale, linking RNA methylation to tumour suppression mechanisms.

Detection

• A CRISPR-integrated nonlinear optical biosensing platform combines DNA-programmable nanostructures with monolayer MoS₂ metasurfaces, using quantum dot–FRET pathways to boost second-harmonic generation signals by over 124-fold. The CRISPR system acts as a molecular switch, modulating signal intensity upon target recognition to achieve microRNA detection limits of 168 zM – over six orders of magnitude beyond conventional optical biosensors – with single-base discrimination and superior diagnostic performance validated in clinical lung cancer samples.
• The PRICE system combines PNA blockers with CRISPR-Cas13a to selectively detect single-nucleotide variants in miRNA without amplification. PNAs inhibit non-target miRNAs, allowing only target miRNAs to activate Cas13a and produce a fluorescent signal with ~10 fM sensitivity. This enables generalised, precise miRNA SNV profiling in biological samples, offering a clinically relevant tool for cancer diagnostics and mechanistic insights.

Reviews

• Toward precision immunotherapy: In vivo gene editing of T, NK, and myeloid cells. This review discusses the development of CRISPR-Cas–enabled in vivo immune engineering strategies to reprogramme immune cells directly within patients for cancer therapy, highlighting emerging delivery approaches and the key translational challenges that must be addressed for safe and effective clinical application.
• CRISPR-Based Diagnostics for Infectious Diseases: Mechanisms, Advancements and Clinical Transformation Prospects. This review evaluates the development of CRISPR-Cas–based molecular diagnostics for infectious diseases, outlining their mechanistic basis and clinical promise while considering the practical and translational challenges that shape their future deployment.

News from CRISPR Medicine News

• On Wednesday, we published a double interview on a bold idea: bringing CRISPR out of the bloodstream and onto the skin. Epithelica’s leadership discusses topical base editing, durability, IP strategy, and whether gene editing is edging closer to becoming a repeatable dermatology treatment.