CRISPR-IMPRINT for rapid and selective DNA methylation

This technology is an epigenetic editing platform that enables rapid, efficient and selective methylation of targeted DNA regions.

Unmet Need: Rapid and reliable DNA methylation editors

DNA methylation is a fundamental epigenetic language that regulates a vast array of biological processes by selectively turning genes on or off, and abnormal methylation is implicated in numerous human diseases. Despite their promise, current CRISPR-based DNA methylation editors are still constrained by slow editing kinetics, off-target activity, and cytotoxicity, which substantially limit their broad applicability.

The Technology: Rapid and selective DNA methylation editor with low cytotoxicity

This technology is a DNA methylation editing platform, CRISPR-IMPRINT, that embeds an engineered bacterial cytosine methyltransferase in the CRISPR-dCas9 system. It enables rapid, efficient methylation editing within hours, while reducing off-target activity and cytotoxicity compared with existing technologies. In proof-of-concept studies, CRISPR-IMPRINT selectively methylated a pathological disease allele, leading to reduced disease-relevant phenotypes. This technology enables basic epigenetic research and offers potential for therapeutic development.

This technology has been validated in vitro with human cell lines.

Applications:

  • Basic epigenetic research
  • Therapeutic development
  • Cell therapy optimization
  • Disease mechanism modeling
  • Allele-specific regulation studies

Advantages:

  • Efficient, rapid and selective methylation editing
  • Minimal off-target activity
  • Low cytotoxicity

Lead Inventor:

X. Shawn Liu, Ph.D.

Patent Information:

Patent Pending

Related Publications:

*Pan R, Ren J, Chen X, Flores LF, Gonzalez RV, Adonnino AA, Lofts B, Waldo J, Halmai J, Devinsky O, Fink K, Liu XS. “Editing DNA methylation in vivo” Nature Communications. 2025 Dec 10;17:527.

*Qian J, Guan X, Xie B, Xu C, Niu J, Tang X, Li CH, Colecraft HM, Jaenisch R, Liu XS. “Multiplex epigenome editing of MECP2 to rescue Rett syndrome neurons” Science Translational Medicine. 2023 Jan 18;15(679).

Tech Ventures Reference:

Quick Facts:
Tags
AlleleCell therapyCytosineCytotoxicityDNA methylationEpigeneticsMECP2Mathematical optimizationMethyltransferaseRett syndrome
Inventors
Shawn (X.) Liu Ph.D.
Manager
Joan Martinez
Departments
Physiology and Cellular Biophysics
Divisions
Columbia University Medical Center (CUMC)
Reference Number
CU26076
Release Date
2026-08-10