CMN Weekly (27 June 2025) - Your Weekly CRISPR Medicine News

Top picks

• Using double-stranded DNA deaminase toxin A-derived cytosine base editors (DdCBE), researchers introduced and corrected mitochondrial DNA mutations in human cells. Introducing m.15150G > A mutations in liver organoids reduced ATP production proportionally to heteroplasmy levels while correcting m.4291T > C in patient fibroblasts restored mitochondrial function. mRNA-based mitochondrial editing via lipid nanoparticles showed superior efficiency, highlighting the therapeutic potential for mitochondrial diseases and enabling precise disease modelling.
• CRISPR Therapeutics’ CTX310 – a CRISPR-Cas-based therapy targeting the ANGPTL3 gene –demonstrated in Phase 1 trials peak reductions of up to 86% in LDL cholesterol and 82% in triglycerides at the highest dose (0.8 mg/kg). Administered via lipid nanoparticle delivery to the liver, CTX310 showed no clinically significant liver enzyme changes and maintained a favourable safety profile. Complete trial results are anticipated later in 2025.

Research

• Using CRISPR-Cas9, researchers knocked out the endogenous p53 gene in A549 lung adenocarcinoma cells to create TP53-null models, then reintroduced wild-type or hotspot mutant p53 variants. These isogenic lines revealed differential impacts on gene expression and proliferation. Wild-type p53 suppressed growth and induced canonical targets, while mutants such as R273H and R175H showed gain-of-function profiles, highlighting mutation-specific oncogenic mechanisms.
• A tamoxifen-inducible CRISPRa/i system has been developed to enable reversible and rapid control of gene expression in mammalian cells. The platform offers an alternative to constitutive or doxycycline-based regulation, with reduced background activity and faster responsiveness. The new study presents inducible CRISPR activation and interference (iCRISPRa/i) systems by engineering CRISPRa/i components with modified human oestrogen receptor domains (ERT2).
• Researchers have used CRISPR-dependent adenine base editing in human T cells to functionally classify over 100 genetic variants associated with activated PI3Kδ syndrome (APDS), a primary immune disorder. They mapped variant effects onto the PI3Kδ signalling pathway, validated functional impacts, and demonstrated that leniolisib (a PI3Kδ inhibitor) corrects abnormal T-cell activity. This scalable method highlights a promising approach for clarifying diagnostic uncertainty and refining precision treatments in immunological diseases.

Screening

• A high-throughput prime editing screen in human cells reveals that some synonymous mutations, previously considered functionally neutral, can have a significant impact on cellular fitness. Using engineered pegRNA libraries, this study identified and characterised hundreds of such mutations, uncovering mechanisms that include aberrant splicing, RNA folding alterations, and changes in translation efficiency.
• Researchers have used CRISPR screening to identify asperigimycins, a new class of fungal ribosomally synthesised and post-translationally modified peptides (RiPPs) with a heptacyclic scaffold including a benzofuranoindoline core. They showed that the anticancer activity of lipid-modified asperigimycin B (notably 2-L6) depends on the SLC46A3 transporter for cellular uptake. 2-L6 displayed nanomolar potency against leukaemia cells, outperforming its parent compound by over 100-fold.

Industry

• The Broad Institute has successfully appealed the European Patent Office’s decision to revoke its pivotal CRISPR-Cas patent over disputed priority claims. Following recent European legal revisions affecting patent priority rights, the case now returns to a lower court to reassess patent validity based on novelty and inventive criteria, reinstating Broad’s position in the ongoing European CRISPR-Cas patent dispute.
• Vor Bio has secured approximately $175 million through a private placement (PIPE), issuing pre-funded warrants for 700 million shares at $0.25 per warrant. Key investors include RA Capital, Mingxin Capital, and Venrock Healthcare Capital Partners. Funds will advance Vor Bio’s clinical pipeline, notably telitacicept, a dual-target fusion protein currently in Phase 3 trials for autoantibody-driven diseases.
• Perceptive Advisors’ acquisition of Synthego, a leader in CRISPR solutions, has been cleared to close in July. The deal provides Synthego enhanced financial stability for expansion and innovation in CRISPR technologies, maintaining U.S.-based manufacturing of guide RNA therapies. Synthego’s operations, leadership, and client support remain uninterrupted, with anticipated staff growth and the reinforcement of capabilities in cell and gene therapy development for curative treatments.

Clinical and preclinical

• Precision BioSciences’ ARCUS gene-editing therapy, PBGENE-DMD, has received FDA Rare Pediatric Disease Designation for the treatment of Duchenne muscular dystrophy (DMD). PBGENE-DMD precisely excises dystrophin gene exons 45-55, potentially benefiting over 60% of DMD patients. Preclinical studies demonstrate significant and durable functional dystrophin restoration in muscles, including the cardiac and skeletal muscle systems, as well as the use of stem cells. Clinical trials are anticipated to begin in 2026, with the potential for a Priority Review Voucher upon approval.

Reviews

• How and when organisms edit their own genomes. This review explores the diverse mechanisms by which organisms deliberately edit their own genomes, highlighting shared genetic strategies across taxa and suggesting that additional editing systems likely exist in understudied host-pathogen contexts.
• CRISPR/Cas9 and iPSC-Based Therapeutic Approaches in Alzheimer’s Disease. This review discusses the potential and limitations of using CRISPR-Cas9 and human-induced pluripotent stem cells (iPSCs) to model Alzheimer’s disease and uncover therapeutic targets, highlighting their promise for precision medicine while acknowledging significant technical and translational challenges.
• A review on the mechanism and potential diagnostic application of CRISPR/Cas13a system. This review examines the structure, mechanism, and diagnostic applications of the CRISPR-Cas13a system, highlighting its advantages over traditional methods and its potential as a rapid, sensitive, and portable RNA detection platform.
• Advancing Cholangiocarcinoma Diagnosis: The Role of Liquid Biopsy and CRISPR/Cas Systems in Biomarker Detection. This review examines the integration of liquid biopsy technologies with CRISPR-Cas systems for cholangiocarcinoma diagnosis, highlighting the RACE platform's ability to detect extracellular vesicle-derived microRNAs with high sensitivity and single-nucleotide specificity.

Detection

• Researchers developed a CRISPR-Cas13a-based MIRA assay for monkeypox detection, achieving a sensitivity of 14.4 copies/mL and 100% clinical specificity and sensitivity. The assay outperformed qPCR in three cases and enabled visual detection via lateral flow strips, identifying positives with Ct values as high as 39. An adjunct PCR assay distinguished Clades I and II within 40 minutes, aiding precise epidemiological monitoring.
• A one-pot CRISPR-Cas12a assay combined with RPA enables rapid, instrument-free detection of tick-borne severe fever with thrombocytopenia syndrome virus (SFTSV) within 45 minutes. Targeting the viral S gene, the assay achieves a detection limit of 11.7 copies per reaction and shows no cross-reactivity. Among 46 samples, it demonstrated 89.13% agreement with PCR, providing a practical and sensitive alternative for RNA virus diagnostics in resource-limited settings.

News from CRISPR Medicine News

• Today, Friday, our sister site WeDoCRISPR posted a reminder that CRISPR is far more than a genome-cutting tool. Described as the “Eevee” of molecular biology, it highlights how fusions and tweaks transform CRISPR into diverse functions—from gene activation and precise base editing to epigenetic tuning and live-cell imaging. The post celebrates CRISPR as a continually evolving platform for genetic innovation.