Single-Molecule Epigenetic Analysis of Plasma Isolated Nucleosomes for Colon Cancer Diagnostics

The analysis of cell-free DNA (cfDNA) in plasma represents a rapidly advancing field in medicine, with developing methods aiming to utilize it for diagnostics of cancer and additional pathologies.

Most liquid biopsy methods are sequencing-based and provide limited information, usually relying on the detection of rare cancer-associated mutations. Therefore, they are costly and highly limited in their sensitivity.

Importantly, blood cfDNA consists predominantly in the form of nucleosomes, which maintain their tissue-specific epigenetic modifications. Thus far, this rich epigenetic information has been inaccessible due to technical limitations.

We developed EPINuc, a novel single-molecule multi-parametric-based assay to comprehensively profile the Epigenetics of Plasma Isolated Nucleosomes.

Our approach is based on a technology we developed (Shema et al., Science), which allows high resolution profiling of combinatorial modification states on millions of individual nucleosomes by single-molecule imaging. EPINuc is unique in its capacity to generate multi-layered information from very limited liquid biopsy material.

As proof of concept, we applied it to diagnose colorectal cancer (CRC), which is one of the most common cancers worldwide, necessitating expensive and invasive screening tests for all adults older than 50.

Strikingly, EPINuc revealed significant differences in the epigenetic states and protein biomarkers’ levels between healthy individuals versus CRC patients.In this PoC, we will optimize EPINuc to generate holistic data from plasma-isolated nucleosomes that is expected to identify cancers early from a routine blood test, without the need for invasive measures.

This technology has significant commercialization value for the liquid biopsy industry.

We will develop a commercialization strategy and network with potential collaborators, customers and investors to spin out the innovation as a successful assay technology business.