Filters
Availability
Publication Year
Resource Type
Faculty
School/Institute
Publication Search Results
Sort
Results per page
1 - 1 of 1
-
(2024)ThesisGene electrotransfer is a technique whereby an electric field is applied to a target tissue to permeabilise the cells, allowing for plasmid DNA/RNA to be taken up and expressed, for a range of therapeutic applications. The BaDGE®project group at UNSW has begun developing new hardware and strategies to improve on current methods for electrotransfer, with an aim to target anatomical regions previously inaccessible with current techniques. One such application is the globus pallidus region of the brain, for treating Parkinson’s disease with plasmids encoding neuromodulating molecules. This thesis details the design, development, characterisation, and in vivo validation of a new device and protocols for improved electrotransfer. This device which could be operated untethered, consisted of integrated fluid and electric pulse delivery via the use of concentric needles, and was shown to have reliable electrical discharge, low fluid dead space, and low bilayer voltage losses. Several methods to enhance the operation of the device were tested and validated both in vitro and in vivo, including the use of quasimonopolar current steering to shape the local electric fields, and the use of sucrose solution for suspending the DNA in order to modify local resistivity and increase field strengths. Finally, a computational model was constructed to demonstrate the operation of this device in an accurately modelled human brain, incorporating findings from earlier experimental results. These experiments and models predicted that the hardware designed in this thesis could be used to achieve substantial transfection in the globus pallidus, especially with the enhancements developed, such that gene electrotransfer could be used as an alternative to current strategies for treating Parkinson’s disease.