Precise Epigenome Therapy Using DNA Methylation and Demethylation Enzymes Fused to CRISPR/Cas9

Hellman Asaf, HUJI, School of Medicine - IMRIC, Developmental Biology and Cancer Research
Meron Nurit, HUJI, School of Medicine - IMRIC


Epigenome editing by DNA methylation or demethylation of regulatory sequences are widely required in medicine and in biomedical research, but current technologies are non-specific and provide unpredictable effects. This technology allows one to modify DNA methylation level at specific genomic sites.

Our Innovation

Targeted DNA demethylation and activation of endogenous genes.

It was demonstrated using TALE-TET1 fusion proteins, but its applicability is restricted by inherent limitations of the TALE genome editing technology.‏ The CRISPR/Cas9 technology recently became the method of choice for genomic editing, having numerous applications in genomic research and is highly demanded in the gene therapy field. This technology combines the proved capability of TET fusion proteins to alter the DNA methylation level and modify the expression level of genes without changing the DNA sequence, with the established flexibility and versatility of the CRISPR/Cas9 genome editing assay.


Tools for epigenome editing, particularly demethylation of desired genomic targets, are highly demanded among biomed companies in the field of developing epigenetic anti-cancer therapy protocols.

New methylome editing assays may be used in a broad spectrum of biomed research and therapeutic applications including, but not limited to:

  • Modification and tuning of gene activity level.
  • Uncover and tune of cancer regulatory networks.
  • Mapping and targeting driving regulatory epimutations.
  • Exposure of cancer cells to the immune system.

Current Development Stage

  • TRL3 Experimental proof of concept
  • Following targeted demethylation of particular sites within KCNE4 and HBB gene regions, methylation levels of the targeted sites were significantly reduced. Based on these results of the inventors are aiming (in the second part of their study) to provide exact examples for the application of the targeted demethylation assay in tuning the regulatory networks of cancer genes.

Patent Status

Published 2019-0100732-A1

Contact for more information:

Keren-Or Amar
VP, Business Development, Healthcare
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