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Effective engineering of the mitochondrial genome

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R43GM125462-01
Agency Tracking Number: R43GM125462
Amount: $224,564.00
Phase: Phase I
Program: SBIR
Solicitation Topic Code: 300
Solicitation Number: PA16-302
Solicitation Year: 2016
Award Year: 2017
Award Start Date (Proposal Award Date): 2017-08-01
Award End Date (Contract End Date): 2019-01-31
Small Business Information
Saint Paul, MN 55104-4179
United States
DUNS: 079960066
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 (617) 582-8184
Business Contact
Phone: (612) 309-7653
Research Institution

This proposal leverages our novel unprecedented and unique method for editing the mitochondrial genome B MoGen has
exclusive license to this technology This proposal will finally provide the final piece to complete the human genome project
from a functional perspective since it has been impossible to make targeted gene knockouts in the mitochondrial genome
until now This is critically important given that the mitochondria play pivotal roles in human biology and disease Indeed
there are many mitochondrial genetic diseases that have been impossible to model in isogenic pairs of cells In this
proposal we will generate human cell lines including a human induced pluripotent stem iPS cell line that carry a
mitochondrial genome deletion present in the most common human mitochondrial genetic disease called Kearns Sayre
Syndrome KSS We will employ our mitoTALE nickases to introduce kb deletions spanning position to position
in the mitochondrial genomes in these cells We will employ our mitoTALENs to induce heteroplasmic shift of the
mitochondrial genomes to those carrying the deletion Secondly we will develop tools to make doxycycline and cumate
inducible mitoTALEN vectors for allowing conditional generation of mitochondrial deletions and induction of heteroplasmic
shift Finally we will generate mitoTALE nickases to target each of the protein encoding components of the mitochondrial
genome and each of the encoded ribosomal RNAs rRNA in both mouse and human cells Project Narrative
Although there have been significant advancements in gene editing over the past two decades none have been able to
precisely edit the mitochondrial genome until now The goal of the proposed project is to use mitochondrial gene editing
technology we have acquired to generate a set of tools and reagents to create human and mouse cell lines that carry a
deletion in each protein and ribosomal RNA encoded on the mitochondrial genome The result of this proposal will provide
researchers with a novel set of tools necessary to better understand and interrogate mitochondria biology and disease

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

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