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A Platform Technology for High-Throughput Screening of Gene Regulatory Elements

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R41GM119914-01A1
Agency Tracking Number: R41GM119914
Amount: $224,881.00
Phase: Phase I
Program: STTR
Solicitation Topic Code: 200
Solicitation Number: PA15-270
Solicitation Year: 2016
Award Year: 2016
Award Start Date (Proposal Award Date): 2016-09-01
Award End Date (Contract End Date): 2017-08-31
Small Business Information
Durham, NC 27712-3006
United States
DUNS: 079953960
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 (919) 684-8196
Business Contact
Phone: (202) 431-0169
Research Institution

Project Summary Abstract
The goal of this proposal is to develop a novel high throughput platform for understanding gene regulatory
elements in order to identify new drug targets for common diseases The human genome encodes
approximately genes Understanding how those genes are regulated and how this correlates to
complex cell phenotypes has long been a major focus of our team Follow up projects to the Human Genome
Project such as the NIH funded Encyclopedia of DNA Elements ENCODE and the Roadmap Epigenomics
Project have identified millions of putative regulatory elements across the human genome for many human cell
types and tissues Importantly genome wide association GWA studies have strongly indicated that non
coding regulatory elements determine the gene expression patterns responsible for most complex diseases
including cancer cardiovascular disease diabetes and neurological disorders However the function of these
regulatory elements and their relationships to these disease phenotype are largely unknown Additionally
conventional screening technologies for perturbing cellular processes such as small molecules and RNA
interference cannot directly target genomic regulatory elements To address this critical limitation and
illuminate the fundamental genomic basis of these cell phenotypes we have recently developed epigenome
editing technologies for directly and precisely activating and repressing genomic regulatory elements in their
natural chromosomal location More recently we have developed a novel and robust method for using these
tools for high throughput identification and quantification of gene regulatory element activity Here we propose
to apply these methods to the discovery and validation of regulatory elements associated with cancer and
cardiovascular disease as demonstration of this novel platform technology for understanding the genetic basis
of complex disease This technology will be critical to translating modern advances in genetics and genomics
into new drug targets diagnostics and personalized medicine catered to each patient genome
Project Narrative
The purpose of this STTR Phase I application is to develop novel methods to identify and characterize gene
regulatory elements and non coding DNA mutations associated with complex disease with the goal of
discovering new classes of drug targets and developing functionally informed diagnostics The academic
partner Duke University has accumulated years of experience with characterizing regulatory elements and
DNA variants using genome and epigenome editing strategies The small business partner Element
Genomics Inc will be involved in developing novel high throughput methods and bioinformatics pipelines to
robustly characterize andapos s of regulatory elements from any region of the genome and will show how
perturbing these regulatory elements contributes to altered phenotype We propose to develop these methods
by focusing on two model genes that have been shown to be involved in human disease The results from
these Phase I studies will be used for future Phase II studies to identify novel small molecule drugs that impact
the expression of those genes

* Information listed above is at the time of submission. *

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