CRISPR Technology Advances: Off-Target Benchmark, New Data, and Licensing Deal
IDT's study showed UNCOVERseq achieved 97.6% sensitivity and 78% precision for CRISPR off-target nomination. Scribe will present new data at ASGCT and EAS, including STX-1150. Watchmaker licensed CRISPR-Cas9 IP for NGS normalization.
Recent announcements highlight significant advances across the CRISPR landscape, spanning off-target detection, therapeutic development, and sequencing workflows. Integrated DNA Technologies (IDT), a Danaher company, published a peer-reviewed study in Nature Communications establishing a new analytical performance benchmark for CRISPR off-target nomination, reporting that its UNCOVERseq workflow achieved the strongest combined sensitivity and precision among methods evaluated. Scribe Therapeutics also announced it will present new data on its engineered CRISPR platforms at upcoming scientific meetings, and Watchmaker Genomics licensed foundational CRISPR-Cas9 intellectual property from Caribou Biosciences for use in next-generation sequencing (NGS) library preparation.
The IDT-led study, titled 'UNCOVERseq Enables Sensitive and Controlled Gene Editing Off-Target Nomination Across CRISPR-Cas Modalities and Systems,' found that UNCOVERseq delivered 97.6% analytical sensitivity and 78% precision across the two guide RNAs used for comparison—the strongest combined sensitivity and precision among the methods evaluated. The research, conducted with University of California, San Francisco scientists, created an inter-method benchmarking dataset based on targeted confirmation of potential off-target sites, allowing performance to be assessed against empirically observed editing rather than the size of a method's candidate list.
The study also defines operating conditions that influence off-target nomination, including biological replication, genomic DNA input, sequencing depth, library preparation, alignment criteria, and process controls. The researchers found that insufficient operating conditions can limit method performance, while low-precision approaches may generate large candidate lists that increase downstream confirmation burden, time, and cost. The publication comes as the U.S. Food and Drug Administration considers draft guidance on the use of next-generation sequencing and bioinformatics in non-clinical safety studies for human genome editing products; the study was conducted independently and does not represent regulatory guidance.
Scribe Therapeutics will participate in the 29th American Society of Gene & Cell Therapy (ASGCT) Annual Meeting, taking place May 11-15 in Boston and virtually, and the 94th European Atherosclerosis Society (EAS) Congress, taking place May 24-27 in Athens, Greece. At ASGCT, Scribe will deliver two oral presentations and one workshop presentation highlighting advances to its ELXR and XE genome editing technologies, including DeepXE, an AI-enabled CRISPR design platform for predicting editing efficiency for XE-based therapeutics. At the EAS Congress, the company will present late-breaking preclinical data for STX-1150, its PCSK9-targeting epigenetic silencing therapy designed to lower low-density lipoprotein cholesterol (LDL-C) levels without inducing permanent DNA changes.
Watchmaker Genomics announced a non-exclusive license with Caribou Biosciences for certain foundational CRISPR-Cas9 intellectual property for use in NGS library preparation. The company is leveraging CRISPR-Cas9 as a programmable, stoichiometric binding tool to address library normalization, using adapter-specific guides to bind sequencing-ready libraries in a controlled manner and enable standardization of library inputs without extensive quantification. The non-destructive process preserves library integrity and complexity, supports re-sequencing or workflow branching, and is compatible with existing adapters and established pre-sequencing workflows. Watchmaker is further adapting the strategy as a core component of a complete PCR-free whole genome sequencing solution designed for large-scale population studies, newborn screening, and rare disease applications.
Scribe is a biotechnology company developing optimized in vivo CRISPR-based technologies and genetic medicines, with initial programs targeting drivers of atherosclerotic cardiovascular disease such as elevated LDL-C, lipoprotein(a), and triglycerides. The company has formed strategic collaborations with Sanofi and Eli Lilly. Watchmaker Genomics develops high-performance tools for genomic research and clinical applications, focusing on areas including cancer detection, epigenetics, and liquid biopsy.