Direct Genome-Scale Mapping of Endonuclease Activity of the Human LINE-1 ORF2p Endonuclease
Nabsys and the Research Lab of Dr. Martin Taylor, Brown University, Present Data Using the OhmX™ Platform at AGBT 2026
EGM enables the direct detection of endonuclease activity at the genome scale by identifying DNA nicking events on long DNA molecules. This capability addresses challenges associated with mapping endonuclease-induced nicks within complex DNA mixtures. Beyond endonuclease activity, future applications of EGM may enable direct, genome-wide analysis of additional DNA modifications and damage.
The data presented demonstrate the use of EGM to directly measure nick positions generated by the LINE-1 ORF2p endonuclease across the human genome. This approach unlocks sequence-level insight into endonuclease activity associated with the LINE-1 retrotransposon that causes DNA damage and mutagenizes the human genome.
LINE-1 is an autonomous retrotransposon that expands within the genome through an RNA-mediated "copy and paste" mechanism and has written around one-third of the human genome. Approximately 5% of humans harbor a new LINE-1–mediated genomic insertion that is not present in either parent. By generating DNA breaks that can lead to insertions and structural rearrangements, ORF2p activity is increasingly recognized as a driver of genome instability, especially in cancer. Aberrant LINE-1 activity has also been linked to neurodegenerative disease and age-related decline, underscoring the importance of mapping its activity genome-wide.
"Our understanding of the genomic sequences of LINE-1 endonuclease cuts is limited," said Dr. Martin Taylor, Principal Investigator of this study. "Understanding this activity is critical to understanding LINE-1-mediated DNA damage in cancer and insertional mutagenesis in sporadic genetic disease. EGM provides a powerful tool to directly map this critical enzymatic activity genome-wide. We're also very excited about the potential of EGM to be adapted for other assays, such as directly mapping other DNA modifications and binding events."
To perform the assay, DNA molecules treated with ORF2p endonuclease were labeled using the OhmX Velocity Optimized Label and Tagging™ ("VOLT") Whole Genome Kit. Prepared samples were then analyzed using EGM on the OhmX™ Platform to identify and map endonuclease nick sites. Nicking frequency was assessed in a concentration-dependent manner to determine endonuclease activity.
"LINE-1 activity contributes to the pathology of common diseases, including cancer, by inducing inflammation and DNA damage," said
About Nabsys 2.0, LLC
Nabsys is advancing genomics with a clear focus on accessibility and innovation through its proprietary electronic genome mapping (EGM) technology. Implemented on the OhmX™ Platform, EGM integrates precision electronics, nanofluidics, and computational biology to deliver high-resolution insight into genome structure. This approach expands what's possible in cytogenetics, molecular genetics, and cell and gene therapy research, while providing comprehensive structural variation analysis to laboratories of all sizes. The company was founded in 2005 and is based in
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