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A new epigenetic toolbox for inflammation research and drug discovery

Award Number: R44AI162386
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/05/2021
PERIOD OF PERFORMANCE END DATE: 04/30/2024

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A new epigenetic toolbox for inflammation research and drug discovery - PROJECT SUMMARY Gene regulation is controlled in part by histone post-translational modifications (PTMs) on nucleosomes. EpiCypher® is developing fully defined recombinant designer nucleosomes (dNucs) carrying specific histone PTMs to enable epigenetics research and drug development. The power of EpiCypher’s dNuc platform comes from its broad chemical diversity. EpiCypher has commercialized > 100 unique dNucs, covering the most widely studied PTM classes (e.g. lysine methylation / acylation / ubiquitylation, arginine methylation, serine phosphorylation, etc.) and is leveraging the emergent property of this diversity for a range of high value applications: 1) antibody specificity testing (NucleoPlex® antibody validation: e.g. chromatinantibodies.com); 2) ultra-sensitive genomic mapping (CUTANA® CUT&RUN / CUT&Tag assays); and 3) high-throughput biochemical approaches for drug discovery and inhibitor screening (dCypher® assays). To date, EpiCypher’s dNuc technology (and related assay platforms) have been focused on PTMs with known associations with chromatin states and gene regulation. Relying on the field’s largely descriptive histone PTM studies as a guide is an inefficient way for us to expand our discovery platforms and maximize the potential of our nucleosome generating capability to target the most functionally important PTMs. Progress on the discovery side has been hindered by intractability of the multi-copy histone genes for functional genetics studies in mammals (vs. simpler model organisms). Here, EpiCypher is partnering with Dr. Steven Josefowicz (Weill Cornell Medical School) to expand epigenetic tool development for immunology research and biomarker discovery. The innovation of this project is employment of a first-in-class mammalian histone variant H3.3 genetic replacement method to identify orphaned / underappreciated residues (and PTMs) with roles in macrophage stimulation. We will then develop new dNucs containing these PTMs and validate their role in macrophage function. For proof of concept, we developed the histone replacement assay to characterize the role of some highly studied (e.g. H3.3K4, H3.3K36) and underappreciated (H3.3S31) residues in the macrophage stimulation response, and showed the resulting data can immediately be used to guide the delivery of new epigenetic reagents and assays to support the study of immune system function and disease. In Phase II, we will leverage this development pipeline to identify novel resides vital for macrophage stimulation (Aim 1). Next, we will develop a collection of dNucs carrying PTMs on these resides, which will be used in NucleoPlex assays to identify best-in-class antibodies to each target (Aim 2). Finally, we will validate the function of these novel PTMs in immune cell stimulation using CUT&Tag assays as well as share our expanded reagents and capabilities with key opinion leaders for external validation (Aim 3) Together, this work will result in the commercialization of an expanded epigenetics toolbox that will open new avenues of immunological research and drug development.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2023 ( Subtotal = $1,012,272 )
2023	2023	EPICYPHER INC	6 DAVIS DR	DURHAM	NC	27709	DURHAM	USA	Allergy and Infectious Diseases Research	000	3	4/10/2023	NON-COMPETING CONTINUATION	$1,012,272
														Subtotal = $1,012,272

Issue Date FY: 2022 ( Subtotal = $1,012,272 )
2022	2022	EPICYPHER, INC.	6 DAVIS DR	DURHAM	NC	27709	DURHAM	USA	Allergy and Infectious Diseases Research	000	2	4/18/2022	NON-COMPETING CONTINUATION	$1,012,272
														Subtotal = $1,012,272

Issue Date FY: 2021 ( Subtotal = $1,012,272 )
2021	2021	EPICYPHER, INC.	6 DAVIS DR	DURHAM	NC	27709	DURHAM	USA	Allergy and Infectious Diseases Research	000	1	5/5/2021	NEW	$1,012,272
														Subtotal = $1,012,272

Grand Total All Awards = $3,036,816

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A new epigenetic toolbox for inflammation research and drug discovery

Award Number: R44AI162386

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 05/05/2021

PERIOD OF PERFORMANCE END DATE: 04/30/2024

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