CAREER: Quantitative Studies of the Rate-Limiting Steps of Retroviral Production and Transduction to Achieve High Levels of Gene Transfer to In Vitro Skin Equivalents
Stelios Andreadis Principal Investigator
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The objective of this project is to identify the rate limiting steps of the processes of retroviral transduction and production and apply the quantitative understanding of these phenomena to optimize retrovirus-mediated gene transfer of human epidermal stem cells. The ultimate goal is to use the technology of gene transfer in tissue engineering of skin equivalents to either impart new functions to cells or enhance existing cellular activities, in order to improve the therapeutic potential of skin substitutes. The project has four main objectives, which include: (1) to investigate the mechanisms of retroviral decay, (2) to investigate why increased the transduction efficiency of viruses is increased by reverse transcription caused by the exposure to dNTP, (3) to extend a previously developed mathematical model describing retroviral transduction to include a more detailed description of the phenomena, and (4) to develop a new technology to increase transduction efficiency.