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CRISPR Cas Systems Delivered by Targeted Nanoparticles to Eradicate Herpesvirus Pathogens

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R43AI131958-01
Agency Tracking Number: R43AI131958
Amount: $306,277.00
Phase: Phase I
Program: SBIR
Solicitation Topic Code: NIAID
Solicitation Number: PA14-307
Timeline
Solicitation Year: 2014
Award Year: 2017
Award Start Date (Proposal Award Date): 2017-04-01
Award End Date (Contract End Date): 2018-03-31
Small Business Information
8 WINDOVER LANE
Coram, NY 11727-1131
United States
DUNS: 078465152
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 BALAJI SITHARAMAN
 (631) 655-4736
 theragnostictechnologies@gmail.com
Business Contact
 JUEE VINAYAK
Phone: (631) 655-4737
Email: theragnostictechnologies@gmail.com
Research Institution
N/A
Abstract

Abstract
Herpesviruses are chronic pathogens that infect for life there is no cure years since the discovery
of the first tumor virus the herpesvirus Epstein Barr virus EBV there exist no specific antivirals for EBV
during its latency phase and there are no vaccines The same holds true for most of the other eight human
herpesviruses This proposal aims to develop novel tools to eradicate oncogenic gamma herpesviruses gHV
in cancer cells
We propose to adapt our existing nanoparticle based platform for the delivery of a DNA based
CRISPR Cas system a powerful tool for targeted genome editing We will target and eliminate key viral
genes and functional sequences of the herpesvirus genome to eradicate infection
Our nanoparticle platform
harnesses the remarkable multifunctional capabilities of the carbon nanoparticle oxidized graphene
nanoribbons O GNRs Our recent in vitro results indicate that these graphene single sheet of graphite
particles can serve as a versatile gene delivery platform to deliver DNA with low cytotoxicity and high
transfection efficiency The overall objective of this project is to engineer an O GNR based platform that will
deliver specific nucleic acids to targeted cells in order to cleave and inactivate a herpesvirus genome
Importantly we will utilize the murine gHV pathogenesis system such that we can move quickly from cell
culture based proof of principle experiments to in vivo validation of virus eradication in an accepted and
validated animal model of gHV infection In Aim we will engineer the O GNR platform to deliver DNA to B
cells In Aim we will Identify the guideRNAs that drive specific editing of the gamma herpesvirus genome
Successful completion of the independent aims of this proposal will allow the consolidation of targeted gene
delivery to B cells Aim with RNA guided editing of the virus genome to drive elimination of the oncogenic
herpesvirus from the latency reservoir Aim The in vitro validation in phase will lead to highly tractable in
vivo studies in an established animal pathogen system during phase Project Narrative
Herpesviruses establish life long infections
that can lead to significant disease and mortality especially in
neonates the elderly and immunocompromised patients
A major challenge for combating herpesvirus
infections is the dormant phase of infection termed latency Since current antivirals only target productive lytic
infection novel therapeutic interventions are needed We propose to apply gene editing technology to make
precise cuts that inactivate the viral genome We will
engineer and validate a nanoparticle platform for the
delivery of nucleic acids that provide the instructions to
eradicate a herpesvirus from an infected cell

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

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