Integrated DNA Technologies (IDT), a Danaher company and global leader in genomics, today announced the publication of a peer-reviewed Nature Communications study establishing a new analytical performance benchmark for CRISPR off-target nomination, providing evidence that can help gene editing developers prioritize biologically relevant sites for downstream confirmation and risk assessment. The study, “UNCOVERseq Enables Sensitive and Controlled Gene Editing Off-Target Nomination Across CRISPR-Cas Modalities and Systems,” found that UNCOVERseq™, IDT’s in cellulo workflow for nominating potential CRISPR off-target editing sites, delivered the strongest combined sensitivity and precision among the methods evaluated. The paper also addresses a critical challenge in therapeutic genome editing: determining whether nomination methods reliably identify biologically relevant sites while producing sufficiently precise results to guide subsequent evaluation. The work reflects IDT’s role in helping scientists move from promising gene-editing ideas to decision-quality evidence that can support responsible development at scale.
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Published in Nature Communications, IDT’s latest research shows UNCOVERseq™ achieved the strongest combined sensitivity and precision among evaluated CRISPR off-target nomination methods, advancing genome editing safety assessment.
As gene editing technologies expand across nucleases, high-fidelity variants and base editors, developers must evaluate the possibility that editing could occur at unintended genomic locations. Although multiple computational, biochemical and cell-based methods are available to nominate potential off-target sites, the field has lacked consistent empirical evidence for comparing their analytical sensitivity, precision and operating requirements.
“The future of gene editing will be advanced by generating clear, reliable evidence that helps developers identify and evaluate potential off-target sites with confidence,” said Gavin Kurgan, Sr. Manager, Bioinformatics Applications Development at IDT, and corresponding author of the study. “By moving the industry conversation from the number of nominated sites to measurable sensitivity, precision and downstream confirmation burden, this study demonstrates how IDT works alongside scientists to solve one of therapeutic genome editing’s hardest challenges and accelerate the path from promising science to responsible impact.”
A new benchmark for decision-quality evidence
In the new study, IDT and University of California, San Francisco scientists created an inter-method benchmarking dataset based on targeted confirmation of potential off-target sites, enabling performance to be assessed against empirically observed editing rather than the size of a method’s candidate list. Across the two guide RNAs used to calculate comparative performance, UNCOVERseq achieved 97.6% analytical sensitivity and 78% precision—the strongest combined sensitivity and precision among the methods evaluated.
The research 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 research team 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. By clarifying the conditions required for reproducible performance, the study provides a framework for advancing off-target assessment with greater speed and certainty without compromising analytical rigor.
Kurgan added, “By working across disciplines to measure sensitivity and precision against empirically confirmed editing—and by establishing the operating parameters that influence those measurements—we hope this work provides scientists, developers and regulators with a practical framework for evaluating off-target nomination strategies with greater confidence.”
Timely evidence for an evolving regulatory landscape
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 draft includes recommendations concerning sequencing strategies, sample selection, analysis parameters, and reporting to evaluate off-target editing and loss of genome integrity in support of IND applications and BLAs. Although the study was conducted independently and does not represent regulatory guidance or endorsement, its empirical comparison of analytical performance and operating conditions contributes timely evidence for scientists and developers evaluating how to respond to emerging expectations.
From broad nomination to focused confirmation
UNCOVERseq is part of IDT’s off-target analysis services, helping gene editing developers move from broad nomination to targeted confirmation with greater confidence. By connecting UNCOVERseq nomination with the rhAmpSeq™ CRISPR Analysis System for confirmation, IDT provides an end-to-end assessment workflow that helps teams prioritize sites for downstream safety evaluation. The study’s authors emphasize that orthogonal methods remain important because different approaches have distinct technical strengths and limitations.
To read the full paper, visit: https://www.doi.org/10.1038/s41467-026-74623-7.
To learn more about IDT’s CRISPR off-target analysis services, visit https://www.idtdna.com/OTservices.
Important use statement: Products and tools described in the study are for research use only and are not intended for diagnostic or therapeutic purposes. The data is for informational use and should not be used as the sole basis for critical decision-making. As stated in the manuscript, the assay procedures described have not undergone full validation and formal design and development activities are ongoing.
About IDT
Building from a strong foundation of innovation, expertise, and reliability, Integrated DNA Technologies (IDT), a Danaher company, has evolved from an oligo manufacturer to a leading genomics solutions provider. We work shoulder-to-shoulder with scientific and global health partners to enable genomics breakthroughs at scale. Our vision of enabling researchers to rapidly move from the lab to life-changing advances reflects our ongoing commitment to a healthier, brighter future for all.
For more information about IDT, visit www.idtdna.com and follow the company on LinkedIn, X, YouTube, Instagram and Bluesky.
Disclaimer: RUO — For research use only. Not for use in diagnostic procedures. Unless otherwise agreed to in writing, IDT does not intend these products to be used in clinical applications and does not warrant their fitness or suitability for any clinical diagnostic use. Purchaser is solely responsible for all decisions regarding the use of these products and any associated regulatory or legal obligations.
About Danaher
Danaher is a leading global life sciences and diagnostics innovator, committed to accelerating the power of science and technology to improve human health. Through our connected ecosystem of industry-leading businesses, we work side by side with customers to solve their most complex scientific and clinical challenges—helping move innovations from discovery to delivery faster for patients who depend on them. Powered by the Danaher Business System, our advanced science and technology and proven ability to innovate help enable faster, more accurate diagnoses and reduce the time, cost, and risk required to discover, develop, and deliver life-changing therapies. Through continuous improvement and operational excellence, our approximately 60,000 associates worldwide are focused on delivering lasting impact and improving quality of life around the world, while building a healthier, more sustainable tomorrow. Explore more at www.danaher.com.
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