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| Project ID/Title: | 07-09. Synthetic polymeric vectors for non-viral delivery of nucleic acids across biological membranes | | Advisor: | W. Keith Jones | | Academic Title: | Assistant Professor | | Department: | Pharmacology & Cell Biophysics | | Department Website: | www.med.uc.edu/pharmacology/ | | Email: | joneswk@uc.edu | | Phone: | 513-558-6573 | | Fax: | 513-558-2269 | | Graduate Program(s): | Pharmacology & Cell Biophysics | | Co-Advisor(s): | Theresa Reineke, Department of Chemistry | | Project Description: | Recent clinical trials employing viral gene therapy agents have revealed the difficulties inherent in this approach. Suitable alternatives for DNA delivery across biological membranes have not been forthcoming. Dr. Reineke’s laboratory developed a series of synthetic polymers (polyglycoamidoamine polymers or PGAA) for nucleic acid binding and delivery across biological membranes. These are more efficient and less cytotoxic that commercially available polymers. Dr. Jones’s laboratory developed a highly efficacious type of transcription factor decoy (concatemeric deoxyribonucleotide decoys or CODN) that specifically bind transcription factors, preventing them from regulating downstream genes. By combining these two novel technologies (CODN/PGAA), we have shown that an exemplar transcription factor can be blocked in cultured cells. Further, the decoy/PGAA can be delivered with high efficiency to the myocardium in vivo and is effective against myocardial infarction in the mouse. The goal is to delineate the mechanism of DNA delivery and to employ CODN/PGAA as a research and clinical therapeutic for delivery of transgenes, siRNA and decoys. |
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