Graduation Year

2015

Document Type

Thesis

Degree

M.S.B.E.

Degree Name

MS in Biomedical Engineering (M.S.B.E.)

Degree Granting Department

Chemical and Biomedical Engineering

Major Professor

Mark Jaroszeski, Ph.D.

Committee Member

Timothy Fawcett, Ph.D.

Committee Member

Andrew Hoff, Ph.D.

Committee Member

Richard Gilbert, Ph.D.

Keywords

electroporation, impedance spectroscopy, topical gene delivery

Abstract

When an electric eld is locally applied to tissues in vivo the uptake of exogenous DNA can be greatly increased. This approach to gene transfer, called electroporation (EP) or gene electro transfer (GET), has potential applications in the treatment of skin disorders, vaccinations, some types of cancer and metabolic diseases. The eect of electric elds on cells and tissues has been studied and related to the uptake of DNA. Tissue impedance changes have been measured as a result of electroporation. The aim of this study is to explore the predictive accuracy of impedance spectroscopy for the success of GET. Mice were used in this study for their histological similarities to human skin. The mice were injected with plasmid DNA coding for luciferase and given one of a series of electroporation treatments varying the number and intensity of the electric pulses delivered. The number of pulses delivered was based upon impedance measurements taken during the EP procedure. Mice were then imaged to quantitatively measure the luminescence resulting from the gene delivery procedure at intervals of 2, 4, 7, 10 and 14 days after treatment to quantitatively determine the biological response to gene electrotransfer. Increased luminescence was noticed in treatment groups compared to injection only groups, and the most eective treatments resulted from a feedback mechanism based upon percentage changes in skin impedance. The relationship between impedance change and gene expression suggested that treatment can be improved based on impedance measurements taken during the EP treatment.

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