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Gene Delivery Agents for Ultrasound-Mediated Transfection

Award Information

Department of Health and Human Services
Award ID:
Program Year/Program:
2007 / SBIR
Agency Tracking Number:
Solicitation Year:
Solicitation Topic Code:
Solicitation Number:
Small Business Information
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Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No
Phase 1
Fiscal Year: 2007
Title: Gene Delivery Agents for Ultrasound-Mediated Transfection
Agency: HHS
Contract: 1R43DK079406-01
Award Amount: $99,867.00


DESCRIPTION (provided by applicant): We propose to develop a novel acoustically activated microbubble gene delivery vehicle for treatment of experimental inflammatory bowel disease. Microbubble ultrasound contrast agents composed of a cationic lipid shell are targeted to the adhesion molecule MAdCAM-1 by a monoclonal antibody immobilized to the surface of the agent. Plasmid DNA is coupled to the cationic surface of the agent via electrostatic interaction. Microbubbles are administered intravenously and accu mulate at sites of intravascular MAdCAM-1 expression, corresponding to inflammatory foci. DNA is released from the agents at the target site by ultrasound-mediated microbubble destruction using a clinical ultrasound scanner. This method has shown efficacy for transfecting reporter genes to perivascular tissue in mice and rats. This strategy offers a safe, non-viral, non-invasive method of delivering genetic material in vivo. Selectivity is accomplished by targeting the agents to a molecular marker of inflam mation, and ultrasound-mediated microbubble destruction is required for release of DNA from the agent surface. The stability of these gene delivery vehicles will be examined to assess the feasibility for commercial scale production of a research-grade tool for gene delivery. The ability of these agents to selectively transfect inflamed bowel will be examined using a luciferase reporter gene and bioluminescence imaging in a mouse model of inflammatory bowel disease. This project will result in the developmen t of a novel and efficient gene delivery tool for pre-clinical research, which can eliminate the need for problematic viral vectors and invasive electroporation techniques. Additionally, this work has the potential to translate into a clinically viable met hod of treatment for inflammatory bowel disease. Gene therapy offers a treatment modality for Crohn's disease, for which only symptomatic treatment is currently available. Ultrasound-mediated microbubble gene delivery is a safe, non-viral, non-invasive and high- efficiency method of transfection. The development of targeted ultrasound-activated microbubble gene delivery vehicles presents a novel and effective method of accomplishing gene transfer in pre-clinical research. This technique will offer an altern ative to viral and invasive electroporation transfection techniques, and offers a potential mode for accomplishing gene delivery in a clinical setting using existing ultrasound equipment.

Principal Investigator:

Joshua J. Rychak

Business Contact:

Joshua J. Rychak
Small Business Information at Submission:

TARGESON, LLC 325 Barracks Hill Road CHARLOTTESVILLE, VA 22901

EIN/Tax ID: 127006058
Number of Employees: N/A
Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No