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Stable Gene Transfer by RNA Delivery

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R43HL135984-01A1
Agency Tracking Number: R43HL135984
Amount: $224,634.00
Phase: Phase I
Program: SBIR
Solicitation Topic Code: NHLBI
Solicitation Number: PA16-302
Solicitation Year: 2016
Award Year: 2017
Award Start Date (Proposal Award Date): 2017-05-01
Award End Date (Contract End Date): 2018-11-30
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
 (763) 639-9213
Business Contact
Phone: (612) 309-7653
Research Institution

Non viral gene delivery is used in most biomedical laboratories for basic research and for many commercial
and medical applications These include basic investigations into gene function modification of cells for the
production of recombinant proteins and generation of genetically modified human cells for cancer therapy e g
chimeric antigen receptor transgenic T cells However the delivery of DNA by transfection for gene transfer is
limited by its extremely high toxicity to many cell types such as hematopoietic stem cells and other blood cell
types e g human T cells Thus gene delivery by DNA transfection is very inefficient except in a subset of cell
lines selected for transfectability e g HEK T cells In contrast delivery of in vitro transcribed mRNA results
in robust gene expression in a very high percentage of cells without toxicity greatly out performing DNA
delivery Unfortunately the transient nature of an mRNA limits the utility of this gene delivery method to
special rare circumstances where a short duration of expression is acceptable But in most gene therapy
settings and in many experiments permanent gene expression is desired In this proposal from B MoGen
Biotechnologies Inc we will establish the feasibiliy our entirely new gene delivery system in which an RNA
molecule is delivered to cells that is then converted to a DNA copy in the cell where it is efficiently integrated
into the genome and expressed This novel system should combine the efficiency and non toxicity of RNA
gene delivery with the permanence of DNA gene delivery The applications of this technology for research are
many including numerous settings where DNA transfection is sub optimal Moreover this technology could
revolutionize therapeutic gene delivery to human cells including correction of genetic diseases in blood stem
cells delivery of chimeric antigen receptor transgenes to T cells and delivery of substrate DNA molecules for
homology dependent repair after targeted nuclease mediated double stranded DNA cutting The technology is
based on a retrotransposon from mice called the Intracisternal Type A Particle IAP which does not exist in
human cells As such it is an ideal RNA based permanent gene delivery vehicle for human cells and could be
applied to tissues in situ Project Narrative
This proposal describes experiments designed to further refine and commercialize a new method for
permanent gene transfer into cells especially primary human cells for the purpose of achieving effective gene
therapy or creating cell based therapies after gene transfer The method is efficient but simple does not
involve use of a virus could be used for in situ gene transfer in vivo and is highly non toxic to cells It uses
delivery of single stranded ribonucleic acid RNA which can be modified to prevent activation of innate
immune responses to achieve permanent gene transfer This method avoids the significant toxicities
associated with delivery of double stranded deoxyribonucleic acid DNA The system is based on a mouse
retrotransposon thus extending transposon based gene delivery to this family of transposable elements for the
first time

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

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