Nanocapsules for transposon therapy in cancer

Award Information
Agency:
Department of Defense
Branch
Army
Amount:
$69,883.00
Award Year:
2005
Program:
SBIR
Phase:
Phase I
Contract:
W81XWH-05-C-0084
Award Id:
73700
Agency Tracking Number:
A043-181-0165
Solicitation Year:
n/a
Solicitation Topic Code:
n/a
Solicitation Number:
n/a
Small Business Information
3180 High Point, Chaska, MN, 55318
Hubzone Owned:
N
Minority Owned:
N
Woman Owned:
N
Duns:
095972415
Principal Investigator:
Gretchen Unger
CSO
(952) 443-3798
gmu@genesegues.com
Business Contact:
Robert Unger
CFO
(952) 443-3798
rtu@genesegues.com
Research Institute:
n/a
Abstract
Viral vectors are used in more than 70% of current gene therapy trials. However, immunogenicity, oncogenicity, and poor tumor transfection efficiencies present significant barriers to clinical success. Sleeping Beauty Transposon (SBT) technology, combined with a targeted, tumor-penetrating, non-viral gene transfer system, offers an alternative approach for therapeutic transgene production with low toxicity. We have developed a non-viral, sub-50 nm capsule formulation platform that condenses and encapsulates macromolecules in protein/peptide capsules for targeted drug delivery. In vitro, we have demonstrated nanocapsule uptake is receptor-mediated via caveolae, supporting the possibility of efficient tumor-targeting and intracellular delivery. In vivo, we have demonstrated the potential of nanocapsules for systemic, targeted, tumor-penetrating delivery of oligonucleotides, and produced expression of SBT plasmids for reporter and therapeutic genes. We propose to demonstrate feasibility of nanoencapsulated SBT plasmids for use in targeted treatment of advanced prostate cancer, by comparing the biodistribution of three nanocapsule coating proteins for tumor-targeting in a syngeneic, orthotopic model of prostate cancer. We will select the most promising coating for future testing with a transposon plasmid being developed to generate siRNA against hyaluronan receptors CD44 and RHAMM-1, which have been shown to play major roles in prostate cancer metastasis and tumor survival.

* information listed above is at the time of submission.

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