CMN Weekly (30 January 2026) - Your Weekly CRISPR Medicine News

Top picks

• Topically applied LNPs containing cytosine base editor eTd-CBE, following laser-assisted microporation, enabled in situ correction of the TGM1 c.877-2A>G mutation causing autosomal recessive congenital ichthyosis (ARCI) in human skin models. This approach restored approximately 12% wild-type sequence and 30% transglutaminase 1 enzyme activity with excellent safety, minimal off-target effects, and no systemic distribution, providing comprehensive preclinical evidence for topical gene editing to treat severe genetic skin disorders.
• Intellia Therapeutics can resume Phase 3 dosing of its in vivo CRISPR-Cas therapy nexiguran ziclumeran (nex-z) after the FDA lifted a clinical hold on MAGNITUDE-2 in ATTRv polyneuropathy. The decision follows protocol amendments and enhanced liver safety monitoring, restoring momentum for one-time TTR gene inactivation despite an ongoing hold in cardiomyopathy.

Research

• Base editing and lentiviral transduction outperformed CRISPR-Cas9 editing in a competitive mouse transplantation model of sickle cell disease. Although all approaches achieved durable HSPC engraftment, base editing and transduction produced greater antisickling activity and editing persistence. The data suggest that newer, cut-free editors may offer superior therapeutic robustness compared to nuclease-based strategies.
• CRISPR-Cas9 editing of EZH2 reduced proliferation, invasion and NF-κB signalling in lung adenocarcinoma cells, inducing differentiation programmes. However, edited cells formed larger tumours in vivo, driven by compensatory upregulation of other Polycomb components. The findings caution that epigenetic targeting of PRC2 may trigger adaptive resistance, complicating translation of EZH2-directed cancer therapies.
• CRISPR-Cas cytosine base editing was refined with TCBE-Umax, and TadA-derived editors optimised for zebrafish were used to precisely model human missense disease variants in vivo. High-efficiency, low-bias biallelic F0 editing enabled direct functional testing of variants of uncertain significance. Proof-of-concept studies resolved pathogenicity for multiple hereditary hearing-loss variants, accelerating genotype–phenotype mapping.
• De novo protein design using artificial intelligence generated new-to-nature anti-CRISPR proteins (AIcrs) that achieved highly potent and specific inhibition of Leptotrichia buccalis CRISPR-Cas13a nuclease activity in bacterial and human cells. This approach overcomes the scarcity of naturally occurring anti-CRISPRs and enables the bespoke design of inhibitors to control CRISPR-Cas tools across research, medicine, agriculture, and microbiology applications.
• CRISPR-Cas interference enabled high-throughput functional mapping of non-coding regulatory elements in primary human T cells. The platform identified enhancers controlling PDCD1, HAVCR2 and TBX21, with combinatorial CRE edits fine-tuning exhaustion markers. Targeting HAVCR2 enhancers outperformed gene knockout in CAR T cells, demonstrating precision regulatory editing as a superior immunotherapy strategy.

Clinical and preclinical

• nChroma Bio has dosed the first patient with CRMA-1001, a CRISPR-Cas–derived epigenetic silencer that methylates HBV cccDNA and integrated viral DNA without genome cutting. The open-label Phase 1/2 trial will assess safety and antiviral durability in chronic hepatitis B, with regulatory approvals enabling study expansion to the UK and New Zealand.

Industry

• Seamless Therapeutics has partnered with Eli Lilly and Company to develop recombinase-based gene editing therapies for genetic hearing loss. The $1.1 billion deal highlights growing industry interest beyond CRISPR-Cas, as Seamless’ platform enables large, precise DNA insertions without reliance on host DNA repair. Lilly gains exclusive rights, validating recombinases as a complementary modality in genetic medicine.
• Genenta Science is deprioritising biotech as it pivots toward defence-sector consolidation, repositioning its Temferon programme as a partnered asset. Temferon is a cell therapy, not a gene-editing approach, and its glioblastoma trial will continue, while new studies are paused. The platform is now being marketed for capital-efficient pharma partnerships rather than internal expansion.

Delivery

• CRISPR-Cas9 delivery was improved using engineered endogenous-like extracellular vesicles that package Cas9 RNPs via Lamp2b sorting. Targeting the anti-apoptotic gene Mcl1 induced tumour cell apoptosis and suppressed cervical cancer growth in vivo. The study positions EV-based Cas9 RNP delivery as a scalable strategy to overcome key limitations in CRISPR-Cas cancer therapeutics.
• CRISPR-Cas9 plasmid DNA encapsulated in lipid nanoparticles (90 nm) prepared via a microfluidic system achieved CDK4/6 gene knockout in cancer cells, inducing apoptosis and significantly reducing CDK4/6 expression. In vivo administration at 0.5 μg reduced tumour size and increased median survival from 31 to 51 days, whilst 1 μg exhibited toxicity, demonstrating a promising gene-editing strategy for cancer treatment requiring dosing optimisation.
• Non-viral lipid nanoparticles enabled intracellular delivery and transcription of the full-length EYS gene (~11.6 kb), overcoming viral size limits in inherited retinal disease. An optimised KC2/DOPC LNP achieved stable nuclear plasmid delivery and expression in RPE cells and ex vivo retinal explants. The work establishes LNPs as a viable route for large-gene augmentation therapies.

Screening

• CRISPR activation screens identified genetic pathways regulating cancer-associated Siglec-binding glycans, revealing that Siglec ligand expression is controlled by competition between genes that catalyse α2-3 sialylation and GlcNAcylation of galactose residues, with CD24 dispensable for Siglec-10 binding. The study identified sulfotransferase GAL3ST4 as a potential driver of immune evasion in glioma cells, providing a genomic atlas of cancer glycosylation and actionable immunotherapy targets.
• CRISPR-Cas knockout screening in vivo identified the SAGA chromatin-modifying complex as a cell-intrinsic regulator of hematopoiesis. Loss of Tada2b or Taf5l disrupted H3K9 acetylation and H2B ubiquitination, impairing stem cell output and skewing lineage commitment. The findings link epigenetic control of interferon signalling and mitochondrial function to blood production and myelodysplastic disease states.
• A genome-wide CRISPRi screen in iPSC-derived human neurons identified cellular factors controlling tau aggregate accumulation, including UFMylation, GPI anchor biosynthesis, and the E3 ubiquitin ligase CRL5SOCS4, which ubiquitinates tau and correlates with tauopathy resilience. Mitochondrial dysfunction promoted proteasomal tau misprocessing, revealing proteostasis principles and potential therapeutic targets for Alzheimer's disease and frontotemporal dementia.
• Genome-wide CRISPR screens in isogenic cell lines have identified synthetic lethal targets across 15 frequently altered cancer drivers, offering new therapeutic opportunities for tumours with traditionally undruggable mutations. The study by researchers from Repare Therapeutics validates several novel interactions, including GFPT1 for ARID1A-deficient cancers and expands the therapeutic potential of PKMYT1 inhibition to FBXW7-mutated tumours.
• A genome-wide CRISPR knockout screen in HepG2/C3A human liver cells identified 340 genes that modulate PFOS-induced cytotoxicity, with disruption of SLC6A9 (encoding the glycine transporter GlyT1) and CPSF2 conferring resistance to PFOS exposure. Molecular docking predicted direct PFOS binding to GlyT1, whilst candidate genes were enriched for cancer and liver disease associations alongside DNA damage response and cell cycle pathways, providing mechanistic insights and potential mitigation targets for PFOS toxicity.
• CRISPR-Cas9 pooled screening in immunised mice mapped cell-intrinsic regulators of B cell activation within the splenic microenvironment. An EcoR-enhanced lentiviral system enabled in vivo editing of naïve B cells, identifying 41 positive and negative regulators of plasmablast differentiation. The hits reveal new adhesion, signalling, and metabolic pathways that shape antibody-producing immune responses.

Detection

• A dual-target visual detection platform combining recombinase polymerase amplification, CRISPR-Cas12a, and lateral flow test strips with multicoloured microspheres achieved simultaneous detection of Staphylococcus aureus and Vibrio parahaemolyticus with 50 CFU/mL sensitivity within 42 minutes. The platform demonstrated good specificity and accuracy in complex matrices, providing a rapid, adaptable solution for on-site detection of foodborne pathogens.

Perspectives and comments

• In an interview with CRISPR Medicine News, Cellectis is positioning non-viral TALEN editing as a commercial differentiator, reporting ~40–49% gene insertion and five-fold superior engraftment versus AAV in stem cells. Vice President Julien Valton highlights scalable cssDNA manufacturing, reduced safety risk, and durable cell correction as strategic advantages over CRISPR-heavy, litigation-exposed competitors.
• A Perspective in Chemistry World discusses how the UK’s first approved CRISPR-Cas therapy, Casgevy, has delivered strong clinical benefit but limited real-world reach. High cost, intensive conditioning, and specialist-centre bottlenecks constrain uptake, while questions about toxicity and durability persist. The experience underscores that ex vivo CRISPR-Cas works—but scalable, in vivo editing will be needed to turn regulatory milestones into population-level impact.
• Inside Precision Medicine reports from the 2026 J.P. Morgan Healthcare Conference, that gene editing has shifted from platform bravado to commercial realism. Executives at Mammoth Biosciences, Caribou Biosciences, Stylus Medicine and RheumaGen emphasised manufacturability, access and cost over novelty. Whether via CRISPR-Cas or recombinases, success now hinges on scalable delivery, clinical parity and payer viability—signalling gene editing’s transition from experimental promise to accountable medicine.
• In a public lecture, Hong Li from the Van Andel Institute outlines how CRISPR-Cas editing is being repurposed beyond double-strand DNA cuts, including gene repression/activation, base and prime editing, and targeted epigenetic modulation via fusion proteins. She highlighted a Van Andel programme to engineer a methylation-sensitive Cas9 (AceCas9), using cryo-EM-guided design and directed evolution to boost activity while retaining discrimination of DNA methylation—aiming for safer, cancer-selective genome targeting.

Reviews

• Nanocarrier-mediated CRISPR-Cas delivery: a novel approach against antibiotic-resistant superbugs. This review explores how CRISPR-Cas systems can be harnessed to combat antibiotic resistance, with a particular focus on their mechanisms, antibacterial applications, and the promise of nanocarrier-based delivery strategies to overcome current challenges in clinical translation.