Quantitative and highly versatile chromatin accessibility platform - PROJECT SUMMARY
Chromatin structure can directly regulate gene transcription by local nucleosome positioning /
accessibility. Chromatin accessibility assays thus provide a powerful insight to transcriptional activity.
The ability to compare chromatin accessibility in healthy and diseased tissue is a major drive: changes in this
landscape are associated with a range of human pathologies including cancer, neurological disorders, and aging.
However, current chromatin accessibility assays (e.g. ATAC-seq) lack compatibility with both fixed and native
(i.e. unfixed) samples. Moreover, it remains challenging to normalize samples for cross-study comparisons,
which significantly limits the development of epigenetics-focused drugs and undermines their future clinical
dissection (e.g. biomarker development).
Here, EpiCypher is partnering with New England Biolabs (NEB) to commercialize UniNicE-seqTM
(Universal Nicking Enzyme Assisted Sequencing), a breakthrough chromatin accessibility platform. In
contrast to current technologies, UniNicE-seq is fully compatible with native and fixed sample workflows, as well
as being highly sensitive and requiring significantly less sequencing depth (>10-fold vs. ATAC-seq). The
innovation of this technology is the application of DNA nicking and polymerase enzymes to incorporate
biotin-labeled nucleotides into accessible chromatin regions for subsequent DNA purification, library
sequencing, and genomic mapping. We have successfully used this approach to reliably generate high quality
chromatin accessibility maps in both fixed and native cells. Importantly, these datasets corroborate those
generated by current approaches (ATAC-seq and DNase-seq), demonstrating strong proof of concept for
UniNicE-seq. Here, our goal is to commercialize UniNicE-seq kits and assay services. EpiCypher is an
industry leader in the development of spike-in controls for epigenetics-focused genomic analyses. In Aim 1, we
will leverage this expertise to develop recombinant DNA-based spike-in controls for quantitative UniNicE-seq
assay normalization. This approach is essential to standardize assay methodology and for reliable cross-sample
comparisons. In Aim 2, we will develop and rigorously validate our fully quantitative UniNicE-seq assays in a
range of cell and tissue types, using both native and fixed sample workflows. This Aim will also include the
development of user-friendly bioinformatic tooling to perform “one-click” analyses of UniNicE-seq samples
(including sample normalization and comparisons). In Aim 3, we will develop and validate UniNicE-seq beta kits
for commercial launch and end-to-end assay services. Together, these Aims will provide key reagents, methods,
and application data as we begin to market our UniNicE-seq kits and end-to-end contract research services for
chromatin research and drug discovery.
