CMN Weekly (28 August 2026) - Your Weekly CRISPR Medicine News

Top picks

• HuidaGene Therapeutics has confirmed that a child with Duchenne muscular dystrophy died in August 2025 after receiving its gene-editing therapy HG302 in a Chinese clinical trial. The death was attributed to acute respiratory distress syndrome as part of a severe immune reaction following administration of HG302. The disclosure, prompted by a STAT News investigation, follows the separately revealed death of a girl in an investigator-initiated editing trial and has intensified scrutiny of China's oversight (see below).
• A six-year-old girl in Shanghai died seven days after receiving an intrathecal AAV9 infusion of an adenine base editor – a CRISPR-Cas-derived tool – intended to correct her CHD3 mutation, Science and Retraction Watch report. The bespoke clinical trial, run at Xinhua Hospital by Zilong Qiu with his company Lanqi Xintu Gene Technology, proceeded despite primate toxicology showing liver damage, and the girl's death from thrombotic microangiopathy went unreported. Also, read our take on the incident.

Clinical and preclinical

• Precision BioSciences has dosed the first patient in FUNCTION-DMD, a Phase 1/2 trial of PBGENE-DMD for Duchenne muscular dystrophy. Rather than a CRISPR-Cas nuclease, PBGENE-DMD uses two ARCUS nucleases in a single AAV to excise exons 45-55 of the dystrophin gene, aiming to restore near full-length dystrophin in up to 60% of boys with mutations there. Initial safety data are expected by year-end 2026.
• Fate Therapeutics has treated the first patient in RECLAIM-LN, a potentially registrational Phase 2 trial of FT819 for refractory systemic lupus erythematosus with lupus nephritis. FT819 is an off-the-shelf CD19-directed CAR T-cell therapy manufactured from a clonal, engineered iPSC bank. The open-label, single-arm study will enrol approximately 53 patients, with complete renal response at week 26 as the primary endpoint.
• Beam Therapeutics has dosed the first patient in the global pivotal cohort of its ongoing Phase 1/2 BEAM-302 trial. The liver-targeted base-editing therapy, BEAM-302, is designed to correct the genetic cause of alpha-1 antitrypsin deficiency and address associated lung and liver disease. The cohort is intended to support a potential accelerated approval pathway in the United States.
• Engineered bacteriophages carrying CRISPR-Cas systems that cut essential bacterial genes have been used in a person for the first time to treat malakoplakia. A kidney transplant recipient with progressive Escherichia coli disease received SNIPR Biome's SNIPR001 intravenously, topically and intralesionally alongside antibiotics, with cutaneous lesions healing and the intra-abdominal mass shrinking by 89% at one year, without phage-related adverse events. Also, read our take on the story.
• The FDA has cleared Adicet Bio's IND for ADI-212, an off-the-shelf allogeneic gamma delta CAR T therapy targeting PSMA in metastatic castration-resistant prostate cancer. The candidate pairs membrane-tethered IL-12 armouring with CRISPR-Cas9-mediated disruption of MED12, intended to improve potency in solid tumours. Phase 1 enrolment is expected to begin in the fourth quarter of 2026.
• US regulators have granted RMAT and Fast Track designations to Allogene’s TALEN-edited, allogeneic CD19 CAR T-cell therapy cema-cel for first-line consolidation in large B-cell lymphoma. In an interim analysis of 24 patients, cema-cel cleared minimal residual disease in seven of 12 patients, compared with two of 12 under observation.
• GenAssist Therapeutics has reported one-year data from an investigator-initiated clinical trial of GEN6050X, a base editing therapy that restores dystrophin through CRISPR-Cas-derived base editor-mediated exon skipping while overexpressing ACTG1. Three ambulatory boys with Duchenne muscular dystrophy given a single intravenous dose of GEN6050X showed stable motor function alongside improved cardiac and pulmonary measures, with no new treatment-related findings over follow-up. Also, read our take on the story.
• A $27.7 million ARPA-H award will fund AEGIS, a programme led by the Innovative Genomics Institute to build bespoke CRISPR-Cas base- and prime-editing treatments for children with inborn errors of immunity. Lipid nanoparticles delivered to bone marrow would replace the cell extraction and chemotherapy current approaches require, with the aim of treating ten children within five years at under $200,000 each.

Research

• Researchers at AstraZeneca have used single-cell workflows to map Cas9 off-target activity in vitro and in vivo, showing that individual cells from clonally expanded mouse embryos and embryonic stem cells carry unique off-target and translocation profiles missed by bulk analyses. Editing favoured open, less methylated chromatin, while Cas9-inducible mice showed organ-distinct off-target spectra, repair pathway usage and translocation propensity – arguing for organ-specific safety evaluation preclinically.
• UNCOVERseq, an in cellulo off-target nomination workflow from Integrated DNA Technologies, identifies rare off-target events using defined inputs and analytical process controls, reaching 97.6% sensitivity and 78% precision on a benchmarking dataset. Applied across 192 guide RNAs, it enabled comparative risk assessment for Streptococcus pyogenes Cas9, high-fidelity variants and base editors in haematopoietic stem and progenitor cells, with double-strand break sites ranking concordantly with base editing. Also, read our take on the story.
• A dual AAV9 system pairs drug-inducible Nfyb overexpression with CRISPR-enOsCas12f1-mediated deletion of Nr3c1, the compact editor fitting where Cas9 cannot be packaged. In mice after myocardial infarction, the preclinical combination spurred cardiomyocyte cytokinesis and a more than 28-fold increase in new cardiomyocyte formation on clonal analysis, with regenerative effects also seen in human engineered heart tissues.
• CRISPR-Cas9 was used to introduce the ultra-rare DENND3-p.R534S variant into isogenic human iPSC-derived cardiomyocytes, producing arrhythmic electrical activity, impaired calcium synchrony and delayed excitation-contraction coupling. The variant disrupted BIN1-dependent membrane architecture and nanoscale Cav1.2–RyR2 coupling without altering major calcium-handling protein levels. Genetic or pharmacological Rab11b inhibition restored structural organisation and electrical stability, identifying a potential trafficking-based target requiring in vivo validation.
• Persistent AAV8-delivered CRISPR-Cas9 editing of Pcsk9 or Angptl3 in mouse liver maintained editing for ten months but elicited anti-SaCas9 immunity, inflammatory-cell infiltration and fibrosis. Edited livers also contained mutations enriched in DNA-damage-response genes and guide-independent translocations, despite no detectable changes at predicted off-target sites. No tumours developed, and causal clonal selection remains unproven, limiting extrapolation to transient clinical editing.
• CRISPR-Cas gene-deletion systems were incorporated into a modular toolkit that functioned across phylogenetically diverse, non-model gut Clostridia. Constitutive and inducible promoters enabled robust, tunable gene expression, permitting targeted and reversible control of bacterial trimethylamine and deoxycholic acid production in mice. The tools should facilitate causal studies of microbiota genes and host physiology, while therapeutic microbiome engineering remains prospective.
• Single-cell sci-L3-Strand-seq has revealed that double-strand breaks made by CRISPR-Cas9 are frequently resolved through sister chromatid exchange, a repair outcome invisible to conventional whole-genome sequencing. The work quantifies these events at targeted and repetitive loci, though the proposed involvement of under-replicated regions and TRAIP-like pathways rests on limited numbers of reciprocal daughter-cell pairs and awaits genetic or molecular perturbation.
• CRISPR-Cas9 triple base editor smACGmax simultaneously converts adenine, cytosine and guanine within individual alleles, achieving efficiencies up to 41% across varied sequence contexts with low RNA off-target activity relative to earlier dual editors. It achieved 94% coverage of targeted HBEGF mutagenesis, identifying diphtheria-toxin resistance variants, and resolved SF3B1 variants affecting alternative splicing, enabling higher-diversity saturation mutagenesis screens.
• GEMiNI-seq profiled wild-type and engineered CRISPR-Cas9 and CRISPR-Cas12a nucleases across diverse nucleosome sequences, revealing uniformly reduced cleavage versus naked DNA and strongest inhibition near nucleosome dyads. Activity varied up to 65-fold with nucleosome type. HIFIv1 best balanced sensitivity and specificity on nucleosomal targets, whereas evoSpCas9 performed best on exposed DNA, indicating chromatin context should guide nuclease and target selection.
• A CRISPR-Cas platform packaged gtfB-targeting plasmids in hybrid extracellular vesicles derived from probiotics and Streptococcus mutans. Pathogen-derived vesicles promoted selective uptake, while vesicular ATP enhanced intracellular cleavage and S. mutans elimination. Probiotic vesicle components also altered quorum sensing and immune responses, reportedly restoring microbial balance.
• A dedicated pipeline, CRISPRLungo, handles long-read amplicon sequencing of gene-edited samples, combining unique molecular identifier-based error correction with statistical filtering to separate genuine edits from PCR and sequencing noise. It outperformed existing tools in benchmarking, uncovered previously missed inversions in published CRISPR datasets, and quantified SBDS editing in patient cells despite contaminating reads from the SBDSP1 pseudogene – all via an installation-free web interface.
• Base editors have been designed to disrupt the splice acceptor of HTT exon 13, eliminating the proteolytic cleavage sites that generate toxic N-terminal huntingtin fragments. Delivered to the striatum in a rodent model of Huntington's disease, the editors reduced fragment formation and aggregation, improved functional deficits and limited brain atrophy – preclinical evidence that splice-site base editing can blunt mutant HTT toxicity.
• REPLACE, a homology-independent CRISPR-Cas9 strategy, uses two guide RNAs to excise a defined genomic region and insert a donor lacking homology arms through non-homologous end joining. It achieved 35% exon replacement in primary mouse hepatocytes, swapped a ~27-kb mouse Ace2 interval for the human ACE2 coding region in zygotes, and corrected an LMNA frameshift in patient-derived post-mitotic cardiomyocytes, restoring Lamin A/C expression.

Industry

• Circio and Full Circles Therapeutics have begun a research collaboration pairing Circio's circVec circular RNA expression technology with Full Circles' immune-silent circular single-stranded DNA vectors – the same C4DNA format the company is developing as a non-viral donor for CRISPR-based genome writing. The aim is a re-dosable, non-integrating platform for engineering T and B cells in vivo, assessed for expression and immunogenicity.
• Sangamo Therapeutics selected winning bids worth $163.55 million upfront following a court-supervised bankruptcy auction. Eli Lilly will acquire Sangamo’s zinc-finger, MINT and capsid-delivery platforms and its ST-506 prion programme for $50 million, while PTC Therapeutics will pay $111 million upfront for the Fabry gene therapy isaralgagene civaparvovec, with up to $100 million in milestones. Both transactions remain subject to court approval.
• Epicrispr Biotechnologies has raised $90 million in an oversubscribed Series C financing to advance EPI-321 towards pivotal development for facioscapulohumeral muscular dystrophy and expand its programmable epigenetic-medicine pipeline. The one-time AAV-delivered epigenetic CRISPR therapy is designed to suppress DUX4 expression without altering the DNA sequence. Phase 1/2 enrolment is complete, and the company reports a manageable safety profile, increased lean muscle volume and biomarker evidence of DUX4 suppression.

Q2 2026 financial results

• Vor Bio reports Q2 net loss of $63 million and a cash deposit of $515 million, expected to provide runway into early 2029.
• Vertex Pharmaceuticals reports Q2 net profit of $1.1 billion and a cash deposit of $13.6 billion.
• Prime Medicine reports Q2 net loss of $42 million and a cash deposit of $109 million, expected to provide runway into 2027.
• Precision BioSciences reports Q2 net loss of $33 million and a cash deposit of $112 million.
• Iovance Biotherapeutics reports Q2 net loss of $47 million and a cash deposit of $298 million.
• Intellia Therapeutics reports Q2 net loss of $107 million and a cash deposit of $628 million.
• Fate Therapeutics reports Q2 net loss of $30 million and a cash deposit of $154 million.
• Editas Medicine reports Q2 net loss of $18 million and a cash deposit of $212 million.
• CRISPR Therapeutics reports Q2 net loss of $90 million and a cash deposit of $291 million.
• Cellectis reports Q2 net loss of $22 million and a cash deposit of $167 million.
• Caribou Biosciences reports Q2 net loss of $24 million and a cash deposit of $114 million.
• Beam Therapeutics reports Q2 net loss of $123 million and a cash deposit of $212 million.
• Allogene Therapeutics reports Q2 net loss of $43 million and a cash deposit of $424 million.
• MaxCyte reports Q2 net loss of $24 million and a cash deposit of $114 million.
• Wave Life Sciences reports Q2 net loss of $9 million and a cash deposit of $142 million.
• Korro Bio reports Q2 net loss of $19 million and a cash deposit of $138 million.

Delivery

• CRISPR-Cas12a lipid nanoparticles, functionalised with an Iba-1 antibody and administered intranasally, targeted MAPK9 in brain-infiltrating myeloid cells after traumatic brain injury. The treatment reduced MAPK9 and pro-inflammatory markers while increasing reparative markers in primary macrophages, microglia and injured mouse cortex, attenuating acute neuroinflammation without detected major-organ toxicity. No toxicity in major organs was detected, but neurological benefit, durability and off-target editing were not established.
• Engineering the probiotic Escherichia coli Nissle 1917 to produce CRISPR-Cas9 ribonucleoproteins in situ, researchers created an orally delivered hydrogel that edits NOX2, the gene encoding the gp91phox catalytic subunit that drives reactive oxygen species production. In this preclinical work, the hydrogel lowered NOX2 expression, boosted antioxidant defences and eased inflammation in mice with chemically induced colitis – a route past gastrointestinal degradation of editing components.
• A charge-altering releasable transporter (CART) has been developed to deliver RNA selectively to the corneal endothelium, a non-regenerative layer whose dysfunction underlies several blinding conditions. In mice, the non-viral nanoparticles carried cargoes including circular RNA and CRISPR-Cas9, tolerated redosing and achieved corneal gene editing; they also transfected human donor endothelial cells in vitro and primate cornea in vivo, supporting clinical translation.

Screening

• Genome-wide CRISPR-Cas screens in unprimed and IFN-α-primed THP-1 cells identified distinct positive and negative regulators of cGAS-STING-induced IFNB1 expression, including many not previously linked to interferon signalling. TBL1XR1 and HDAC3, components of the NCoR/SMRT corepressor complex, cooperated to support IFNB1 induction, with HDAC3 promoting TBK1 activation. The dataset may inform studies of interferonopathies, immune deficiencies and cancer.
• Pooled CRISPR-Cas9 knockout and CRISPRi screens across six pancreatic ductal adenocarcinoma cell lines, and in vivo in mice, confirmed that master regulators inferred from single-cell analysis are selectively essential to distinct malignant cell states, with HNF1A among the top dependencies of well-differentiated cells. With barcode lineage tracing and ectopic expression, the work ties three coexisting lineage states – each split by MAPK activity – to targetable dependencies.
• EXCAVATE-HT mines population variant data to design allele-specific CRISPR-Cas guide libraries targeting common SNPs near user-defined loci, including paired guides for genomic excision. Applied to CRX, the tool identified and characterised multiple allele-specific guide sets. Several predicted excisions could cover over 30-fold more patients than targeting one rare disease mutation, although therapeutic efficacy was not demonstrated.

Symposia and events

• CRISPR Medicine News and the Chinese Society of Gene & Cell Therapy will host the virtual symposium In Vivo CRISPR Medicine: From Scientific Promise to Patients at Scale on 3 September 2026, 13:00–15:00 CEST. Four speakers from China and Europe will discuss in vivo editing, RNA delivery, liver-directed genetic medicines, off-target detection and regulatory strategy, followed by a joint panel. Registration is open.