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Epi-seq: Multiplexed ChIP-seq for personalized medicine and drug discovery

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 4R44HG010237-02
Agency Tracking Number: R44HG010237
Amount: $1,817,860.00
Phase: Phase II
Program: SBIR
Solicitation Topic Code: 172
Solicitation Number: PAR16-016
Timeline
Solicitation Year: 2016
Award Year: 2019
Award Start Date (Proposal Award Date): 2019-09-20
Award End Date (Contract End Date): 2021-06-30
Small Business Information
1914 PALOMAR OAKS STE 150
Carlsbad, CA 92008-6509
United States
DUNS: 109145701
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 MARY JELINEK
 (760) 431-1263
 mjelinek@activemotif.com
Business Contact
 THEODORE DEFRANK
Phone: (760) 431-1263
Email: defrank@activemotif.com
Research Institution
N/A
Abstract

SUMMARY
Dysregulation of epigenetic mechanisms is known to play important roles in the development and progression
several disease states including cancer, autoimmune, neurological and inflammatory disorders.
In cancer alone, high frequency mutations in sixty epigenetic regulatory proteins have been identified. Like
genome sequencing, epigenetic information can be elucidated across the entire genome and profiling can be
used to find epigenetic abnormalities that cause or correlate with disease. Computational integration of
genome-wide genetic and epigenetic profiles (epi-genotyping) has enabled identification of novel disease
subgroups, with pediatric neuro-oncology being a notable example. Developing a systems solution that
facilitates integration of epigenetic data sets is key to enabling personalized medicine solutions for pathologies
with epigenetic dependencies. Chromatin immunoprecipitation (ChIP) is the primary method for genome-wide
mapping of DNA associated proteins. In contrast to the tremendous advances in DNA sequencing
technologies, which are approaching the $1,000 genome, ChIP has only had incremental improvements in
work flow, reduction of background and sample size requirements. This SBIR Fast Track proposal intends to
develop Epi-Seq, a high throughput multiplexing ChIP-Seq platform to map functional alterations in the
epigenome on a scale and time frame suitable for clinical and drug screening applications. With automation
compatibility in mind, Epi-Seq combines sample preparation and solubilization of fixed chromatin using PIXUL,
a 96-well plate sonicator capable of shearing 96 chromatin samples in less than 30 minutes, with Transposase-
Assisted Multiplex ChIP-Seq (TAM-ChIP) to functionally annotate the entire genome in a high throughput
format. Multiplexing is achieved with a panel of recombinant AbFlex® ChIP-qualified antibodies targeting
various hallmark features of the epigenetic landscape, each of which has been conjugated to a transposase-
compatible barcoded oligonucleotide via site-directed conjugation. Phase I feasibility will use PIXUL from
human and mouse tissues in Aim1 and compare TAM-ChIP enabled AbFlex® antibodies for key DNA binding
proteins and histone PTMs in traditional and TAM-ChIP-seq methods. Phase II product development efforts will
optimize TAM-ChIP target multiplexing in Aim 3 and Aim 4 efforts will adapt current workflows for automation
compatibility such that a hands-free “sample-to-sequence” workflow is achieved. Phase II efforts will conclude
with alpha-testing by independent laboratories whose feedback will be integrated into subsequent
commercialization efforts by Active Motif. Epi-Seq is an enabling technology with potential accelerate
development of epigenetic diagnostics, prognostic and therapeutics for diverse human pathologies and will be
offered both as a contract service and as a product, sold independently or bundled with the PIXUL instrument.ChIP (chromatin immunoprecipitation) is the keystone method for epigenetics, defined as
regulatory mechanisms which affect heritable changes in cellular phenotypes independent of
DNA sequence. This SBIR Fast Track proposal describes development of Epi-seq, an
automation compatible systems solution which streamlines ChIP, enabling simultaneous
interrogation of multiple targets and provides for integration of complex bioinformatic datasets.
This technology will simplify epigenetics, and will accelerate its adoption in drug discovery and
personalized medicine.

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

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