In Vivo and Ex Vivo Gene Electrotransfer in Ophthalmological Disorders.

The aim of this document is to present an overview of gene electrotransfer in ophthalmological disorders. In order to ensure an adequate variety of the assessed studies, several electronic databases were considered and studies published between January 1998 and December 2021 were analysed. Three investigators carried out data extraction and analysis, focusing on both technical (i.e., electrical protocol, type of electrode, plasmid) and medical (i.e., type of study, threated disease) aspects and highlighting the main differences in terms of results obtained. Moreover, the IGEA experience in the project "Transposon-based, targeted ex vivo gene therapy to treat age-related macular degeneration" (TargetAMD) was reported in the results section. No clinical trial was found on international literature and on ClinicalTrials.gov. Twelve preclinical studies were found including in vivo and ex-vivo applications. The studied showed that electrotransfer could be very efficient for plasmid DNA transfection. Many attempts such as modification of the electric field, buffers and electrodes have been made and the optimization of electric field setting seems to be very important. Using this technique, gene replacement can be designed in cases of retinal inheritance or corneal disease and a wide range of human eye diseases could, in the future, benefitfrom these gene therapy technologies.

Design and Characterization of a Minimally Invasive Bipolar Electrode for Electroporation.

OBJECTIVE: To test a new bipolar electrode for electroporation consisting of a single minimally invasive needle. METHODS: A theoretical study was performed by using Comsol Multiphysics® software. The prototypes of electrode have been tested on potatoes and pigs, adopting an irreversible electroporation protocol. Different applied voltages and different geometries of bipolar electrode prototype have been evaluated. RESULTS: Simulations and pre-clinical tests have shown that the volume of ablated area is mainly influenced by applied voltage, while the diameter of the electrode had a lesser impact, making the goal of minimal-invasiveness possible. The conductive pole's length determined an increase of electroporated volume, while the insulated pole length inversely affects the electroporated volume size and shape; when the insulated pole length decreases, a more regular shape of the electric field is obtained. Moreover, the geometry of the electrode determined a different shape of the electroporated volume. A parenchymal damage in the liver of pigs due to irreversible electroporation protocol was observed. CONCLUSION: The minimally invasive bipolar electrode is able to treat an electroporated volume of about 10 mm in diameter by using a single-needle electrode. Moreover, the geometry and the electric characteristics can be selected to produce ellipsoidal ablation volumes.