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sector_ico_Health_trans Human Health

New chemical tools for enriching and analyzing epigenetic signatures

  • Project Leaders: Fraser Hof
  • Institutions: University of Victoria (UVic)
  • Budget: $200819
  • Program/Competition: Proof of Concept
  • Genome Centre(s): Genome British Columbia
  • Status: Closed

It has been shown that a family of macrocyclic molecules has high affinity and specificity for methylated lysines — epigenetic/gene regulation marks that are especially important in cancer. This project aimed to 1) create prototype solid-phase reagents that will allow the enrichment of methyllysine-containing peptide fragments from proteolyzed mixtures and for ChIP-Seq applications and 2) develop new, cheap, and information-rich enzyme assays based on a novel combination of the macrocycles with fluorescent dyes.

The first market opportunity is in the area of enrichment kits for proteomics/genomics approaches to epigenetics research, and the second is in the creation of high-throughput assays for a large family of epigenetic enzymes that are cancer drug targets.

Both technologies answer the demand of scientists in this area to move away from antibody-based reagents for epigenetics, because they are a) notoriously inconsistent from batch to batch and b) suffer from a well-documented high rate of failed specificity.

Enrichment prototypes were established and tested in proteomics applications in cooperation with the UVic-Genome BC Proteomics Centre. Preliminary results showed liquid chromatography–mass spectrometry (LCMS) based enrichment of methylated peptides from a real proteomics sample to be reproducible and very accurate.

The academic product search team from Merck-Millipore (Temecula, CA), expressed interest in both of the technologies. A Confidential Disclosure Agreement was executed and there were preliminary discussions surrounding the commercialization of Technology 1 — methyllysine enrichment reagents. These discussions were awaiting more solid performance results.

The investigators also worked with Active Motif to optimize performance and pave the way to a licensing deal.