CMN Weekly (26 June 2026) - Your Weekly CRISPR Medicine News

Top picks

• Danish researchers have shown that CRISPR-Cas9-engineered T cells expressing a PD-L1-specific T-cell receptor selectively targeted PD-L1-expressing tumour and immunosuppressive immune cells in vitro. The engineered cells retained potent antitumour activity and could be expanded using peptide-loaded dendritic cells, supporting their potential as an immune-modulating cancer therapy
• Precision Biosciences' in vivo ARCUS gene-editing therapy, PBGENE-HBV, provided the first clinical evidence of directly eliminating and inactivating hepatitis B cccDNA, the viral reservoir that drives infection. Liver biopsies showed reduced cccDNA transcripts, while all evaluable patients lost detectable pgRNA. Early results support the potential for a finite, curative treatment for chronic hepatitis B.

Clinical and preclinical

• CRISPR-Cas therapy CASGEVY showed strong efficacy in children aged 5–11 years with sickle cell disease or transfusion-dependent β-thalassaemia. All evaluable patients achieved sustained freedom from vaso-occlusive crises or transfusion independence. Safety matched previous studies, supporting expansion of use into younger age groups. Also, read our take on the story.
• Prime Medicine received regulatory clearance in New Zealand to begin the first human trial of an in vivo prime editing therapy. PM577a targets the ATP7B H1069Q mutation in Wilson disease, aiming to permanently restore copper transport after a single infusion. The Phase 1/2 study will assess safety, biological activity and early efficacy.
• Prime Medicine’s prime editing therapy PM359 has received FDA RMAT designation for p47phox-deficient chronic granulomatous disease. The decision was supported by Phase 1/2 data showing durable restoration of neutrophil function after a single treatment. The designation could accelerate the development and regulatory review of the gene-edited stem cell therapy.
• Early clinical results suggest that Fate Therapeutics' FT836, an off-the-shelf CAR T-cell therapy derived from induced pluripotent stem cells (iPSCs), may induce tumour regression in heavily pre-treated metastatic colorectal cancer without the need for lymphodepleting conditioning chemotherapy. The engineered cells were also detected within tumour tissue, indicating successful trafficking and persistence in patients with intact immune systems. Also, read our take on the story.
• In a preclinical study, Editas Medicine's in vivo gene editing candidate EDIT-401 reduced LDL cholesterol, lipoprotein(a) and ApoB by ~90% in non-human primates after a single dose. The therapy uses a CRISPR-Cas9 system delivered via LNPs to disrupt the 3' UTR of the LDLR gene, increasing LDL receptor expression and clearance of circulating cholesterol particles.
• CRISPR-Cas therapy lonvo-z from Intellia Therapeutics reduced hereditary angioedema attacks by 87% in a Phase 3 trial, with 62% of treated patients remaining attack- and therapy-free for six months. A single dose inactivated KLKB1, lowering kallikrein levels, and showed a favourable safety profile. Regulatory submission is underway. Also, read our take on the story.
• Updated phase 1 data indicate that a single infusion of Caribou Biosciences' CB-011, an allogeneic anti-BCMA CAR-T cell therapy, can induce deep and durable responses in heavily pretreated patients with relapsed or refractory multiple myeloma (r/r MM). The findings also include an encouraging case study in a patient previously treated with an approved BCMA-directed CAR-T therapy. Also, read our take on the story.
• Beam Therapeutics has received U.S. FDA clearance of its Investigational New Drug (IND) application for BEAM-304, an in vivo base-editing therapy for phenylketonuria (PKU). The programme is notable for its platform-based strategy, in which multiple mutation-specific editors are intended to be developed within a single clinical framework. Also, read our take on the story.

Research

• Researchers have reported the first use of CRISPR-derived base editing to make precise DNA changes in human embryos while avoiding the large chromosomal abnormalities commonly associated with conventional CRISPR-Cas9 editing. The work demonstrates efficient single-base genome editing in early embryos, but also highlights persistent challenges, including mosaicism and off-target effects, and has reignited debate about the future of heritable genome editing.Also, read our take on the story.
• CRISPR-TE is a new method that uses nuclease-inactive CRISPR-Cas13 fused to the m6A reader YTHDF1 to boost translation of specific endogenous mRNAs without editing DNA or RNA sequences. In a mouse model of preeclampsia, targeted enhancement of Vegfa restored placental angiogenesis and improved disease features, demonstrating programmable protein upregulation through epitranscriptomic regulation.
• CRISPR-Cas9 silencing of CD73, combined with photothermal and photodynamic nanotherapy, remodelled the immunosuppressive microenvironment in glioblastoma. Neutrophil-coated nanoparticles crossed the blood–brain barrier, enabling targeted treatment that enhanced antitumour immunity and significantly suppressed tumour growth in preclinical models.
• Researchers have developed EvoPRIME, a new prime-editing screening platform that substantially improves editing efficiency and enables large-scale functional interrogation of disease-associated variants without suppressing DNA mismatch repair. The platform combines a PE3-based editing architecture with Csy4-mediated guide RNA processing and a fluorescence-based enrichment strategy that selectively isolates successfully edited cells. Also, read our take on the story.
• Researchers identified a previously unrecognised CRISPR-Cas9 off-target mechanism in which endogenous RNAs hijack guide RNAs via the tracrRNA. They engineered redesigned guide RNAs that minimise this effect and developed a split-guide RNA platform that enables safer multiplex genome editing and CRISPR-based RNA detection.
• CRISPR-Cas homology-directed repair was boosted by 5′ cyanine-modified donor DNA, increasing editing efficiency up to threefold while improving cell survival in human stem cells. The approach enabled up to 30% precise editing in human blastoids without impairing development, offering a simple strategy to enhance precise genome editing.
• A new CRISPR-based strategy turns cancer cells' own mutant transcripts against them, opening a potential route to one of oncology's most stubborn unsolved problems: the targeting of mutant p53. Rather than attempting to fix or restore the defective protein, the approach uses the mutant transcript itself as a trigger for selective cell death – a conceptual shift that could in principle be applied across a broad range of undruggable cancer mutations. Also, read our take on the study.
• SciPhy is a Bayesian framework that reconstructs cell lineage trees from CRISPR-Cas lineage-tracing data. The method outperformed existing approaches on simulated and experimental datasets, while also estimating cell proliferation rates and developmental dynamics with quantified uncertainty.
• Genome editing was used to insert the viral US2 gene into human induced pluripotent stem cells, selectively reducing HLA-A2 expression while preserving overall HLA-I. The strategy prevented alloreactive T-cell activation without increasing natural killer cell responses, offering a refined approach to immune-evasive cell therapies.
• Researchers created iSCORE-PD, a panel of 65 genome-edited human stem cell lines carrying Parkinson’s disease variants in 11 genes. The resource highlights the precision of CRISPR-Cas and prime editing, with minimal off-target effects, providing a standardised platform for disease modelling.
• A new dual CRISPR-dCas9 epigenome-editing system independently controls H3K27ac and H3K4me3 to dissect their roles in transcription. The study showed H3K4me3 is essential for transcription initiation and elongation, while H3K27ac primarily supports transcriptional activity.

Industry

• YolTech Therapeutics has raised approximately $70 million in Series C financing to advance its in vivo gene-editing pipeline and global development efforts. The company develops LNP-delivered gene-editing therapies based on its HEPDONE editor platform, targeting genetic, metabolic, cardiovascular and autoimmune diseases.
• VectorBuilder and MaxCyte formed a partnership to develop a non-viral gene-delivery platform for ex vivo cell therapies. Combining MiniVec plasmids with electroporation technology improved CAR-T cell viability and gene expression in preliminary studies, with potential applications in CRISPR-Cas editing and other engineered cell therapies.

Delivery

• Optimised lipid nanoparticles boosted in vivo CRISPR-Cas prime editing to 49% in the mouse liver after a single dose. The non-viral system corrected a disease-causing PAH mutation in a phenylketonuria model to potentially curative levels, while reducing off-target editing and supporting repeat dosing.

Screening

• Genome-wide CRISPR knockout screens identified cancer-specific vulnerabilities triggered by inflammatory cytokines. Loss of FITM2 or GPI transamidase genes sensitised tumours to immune checkpoint blockade by increasing interferon-γ-induced stress and tumour cell death, revealing potential therapeutic targets.
• A genome-wide in vivo CRISPR knockout screen identified MED4 as a key suppressor of metastatic reactivation in breast cancer. Loss of a single MED4 allele disrupted enhancer regulation, driving dormant cancer cells to resume growth and suggesting MED4 haploinsufficiency as a biomarker of metastatic relapse.
• Perturb-DBiT enables spatial CRISPR screening by simultaneously mapping sgRNAs and whole-transcriptome RNA in tissue sections. Applied to tumour models, the method linked genetic perturbations to metastasis, clonal evolution and immune interactions, revealing spatial effects on coding and non-coding RNA regulation.

Detection

• A portable CRISPR-Cas13 assay detected mpox virus with 100% sensitivity and specificity in clinical samples from Sierra Leone. The SHINE test identified as few as 10 copies/µL and delivered results in 11–28 minutes, including directly from lesion swabs without nucleic acid extraction.
• A portable CRISPR-Cas9 diagnostic combined LAMP amplification with a microfluidic graphene heater to detect nucleic acids using smartphone power. The low-cost platform detected as few as five target copies per sample, supporting sensitive point-of-care testing in resource-limited settings.

Reviews

• Applications of genome editing technologies in the treatment of human diseases. This review synthesises the mechanisms, capabilities, and delivery strategies of programmable genome-editing platforms across diverse therapeutic applications, assessing ex vivo and in vivo progress and outlining priorities for broader clinical implementation.
• Causal effect estimation from trans-regulatory single-cell CRISPR screens. This review examines how causal effects can be inferred from single-cell CRISPR screens, outlining the assumptions, statistical methods and potential sources of bias involved in interpreting genetic perturbation experiments.
• Genome editing in Africa: A review of technological advances, applications, and the path forward. This review examines the development and application of CRISPR-Cas genome editing in Africa, highlighting advances in agriculture and medicine alongside the regulatory, infrastructural, ethical and funding challenges limiting broader adoption.
• CRISPR application in hematological disorders: from bench to bedside. This review examines how CRISPR-Cas genome editing is transforming hematology, covering approved therapies for inherited blood disorders, emerging applications in blood cancers, advances in editing technologies, and the translational challenges facing broader clinical adoption.
• CRISPR decodes the RNA regulatory network in prostate cancer: A review from mechanisms to precision therapeutics. This review examines how CRISPR-Cas technologies are being used to study RNA regulation in prostate cancer, covering functional genomics, diagnostics and emerging RNA-targeted therapies, while discussing challenges for precision medicine.