A novel epigenetic editing platform - crispr-based gene editing has become mainstream in its popularity because of its approval as a therapeutic

Active Motif, Inc. received a $306,094 Project Grant award from the National Human Genome Research Institute (NHGRI) under the Human Genome Research program (CFDA 93.172), with performance extending from September 20, 2025, through August 31, 2026. The award funds the development of a novel epigenetic editing platform that utilizes an innovative targeting approach to recruit epigenetic effectors to specific genomic loci. This platform enables targeted alterations to the epigenome and directed changes in gene expression without permanent modification of DNA sequences, addressing key safety limitations associated with conventional CRISPR-based gene editing approaches.

The deliverable represents a research-use tool with long-term therapeutic potential. The platform aims to overcome existing limitations in epigenetic editing, including design complexity, binding affinity variability, off-target editing, and delivery challenges inherent to current approaches such as transcription activator-like effectors (TALEs), zinc fingers, and catalytically dead CRISPR systems. By providing a more efficient epigenetic editing methodology, this development advances NHGRI's mission to accelerate scientific breakthroughs through innovative genomic technologies and resources broadly applicable to biomedical research.

Yet, concerns about safety persist since crispr-based therapeutics result in permeant changes to the DNA sequence, which are irreversible if side effects arise. Epigenetic editing, manipulation the epigenome in a targeted way to alter gene expression, in contrast, has become an interesting alternative since IT avoids permanent changes of DNA sequences. However, epigenome editing is an immature field with limited tools available. Options include fusion of epigenetic modifying enzymes to sequence specific DNA targeting proteins such as tales and zinc fingers or a version of crispr that uses an enzymatically dead CAS protein. All of these approaches have limitations including, difficulty in design with extensive cloning effort, variability in binding affinity, off-target editing and delivery challenges based on the large size of the targeting proteins. In this proposal we describe a new epigenetic editing platform that uses a completely novel targeting approach for recruitment of epigenetic effectors to specific genomic loci resulting in targeted alterations to the epigenetic landscape and directed changes in gene expression. This platform will initially be developed as a research use only tool but, in the long term, has the potential for use in a therapeutic setting.