Their ultimate goal is to develop safe, cost-effective, and efficacious vectors for use as DNA vaccines. One problem facing the commercial development of DNA vaccines remains the inability to target large amounts of vector uniformly to nuclei of myofibers in injected muscle. They have shown in vitro that nuclear import of plasmid DNA in non-dividing cells is sequence-specific, requiring portions of the SV40 promoter/enhancer for nuclear uptake. The presence of these SV40 DNA nuclear targeting sequences dramatically increased plasmid nuclear localization and gene expression in non-dividing cells. The next logical step is to proceed to in vivo studies. The SV40 DNA nuclear targeting sequence will be incorporated into Influenza and Chlamydia antigen expressing vectors and tested in vitro in myotubes and dendritic cells and in vivo in mice. Their Phase I goals are to demonstrate the ability of this DNA nuclear targeting sequence to (1) increase gene expression levels by 5 to 10-fold and/or; (2) increase antibody titers by 5 to 10-fold and/or; (3) increase CTL response by 5-10 fold. The feasibility of our approach to lead to better DNA vaccines will be determined by the increased production of neutralizing antibodies against Influenza and Chlamydia, two of our vaccine targets.
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| Anasetti, Claudio (2003) Acquired tolerance to renal allografts in humans. Am J Transplant 3:243-4 |
| Dean, D A; Perkin, R A (2001) Gene therapy: if at first you don't succeed... Am Fam Physician 63:1707, 1710, 1715-6 |
| Dean, D A (2000) Peptide nucleic acids: versatile tools for gene therapy strategies. Adv Drug Deliv Rev 44:81-95 |
