Gene Electrotransfer via Conductivity-Clamped Electric Field Focusing Pivots Sensori-Motor DNA Therapeutics: "A Spoonful of Sugar Helps the Medicine Go Down".

Autor: Pinyon JL; Translational Neuroscience Facility, Department of Physiology, School of Biomedical Sciences, Graduate School of Biomedical Engineering, Tyree Institute for Health Engineering (IHealthE), UNSW, Sydney, NSW, 2052, Australia.; Charles Perkins Centre, School of Medical Sciences, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, 2006, Australia., von Jonquieres G; Translational Neuroscience Facility, Department of Physiology, School of Biomedical Sciences, Graduate School of Biomedical Engineering, Tyree Institute for Health Engineering (IHealthE), UNSW, Sydney, NSW, 2052, Australia., Crawford EN; Translational Neuroscience Facility, Department of Physiology, School of Biomedical Sciences, Graduate School of Biomedical Engineering, Tyree Institute for Health Engineering (IHealthE), UNSW, Sydney, NSW, 2052, Australia., Abed AA; Translational Neuroscience Facility, Department of Physiology, School of Biomedical Sciences, Graduate School of Biomedical Engineering, Tyree Institute for Health Engineering (IHealthE), UNSW, Sydney, NSW, 2052, Australia., Power JM; Translational Neuroscience Facility, Department of Physiology, School of Biomedical Sciences, Graduate School of Biomedical Engineering, Tyree Institute for Health Engineering (IHealthE), UNSW, Sydney, NSW, 2052, Australia., Klugmann M; Translational Neuroscience Facility, Department of Physiology, School of Biomedical Sciences, Graduate School of Biomedical Engineering, Tyree Institute for Health Engineering (IHealthE), UNSW, Sydney, NSW, 2052, Australia., Browne CJ; Translational Neuroscience Facility, Department of Physiology, School of Biomedical Sciences, Graduate School of Biomedical Engineering, Tyree Institute for Health Engineering (IHealthE), UNSW, Sydney, NSW, 2052, Australia.; Medical Sciences, School of Science, Western Sydney University, Sydney, NSW, 2560, Australia., Housley DM; Translational Neuroscience Facility, Department of Physiology, School of Biomedical Sciences, Graduate School of Biomedical Engineering, Tyree Institute for Health Engineering (IHealthE), UNSW, Sydney, NSW, 2052, Australia., Wise AK; Bionics Institute, 384-388 Albert Street, East Melbourne, VIC, 3002, Australia.; Medical Bionics, Department of Otolaryngology, University of Melbourne, Melbourne, VIC, 3002, Australia., Fallon JB; Bionics Institute, 384-388 Albert Street, East Melbourne, VIC, 3002, Australia.; Medical Bionics, Department of Otolaryngology, University of Melbourne, Melbourne, VIC, 3002, Australia., Shepherd RK; Bionics Institute, 384-388 Albert Street, East Melbourne, VIC, 3002, Australia.; Medical Bionics, Department of Otolaryngology, University of Melbourne, Melbourne, VIC, 3002, Australia., Lin JY; Tasmanian School of Medicine, University of Tasmania, Hobart, TAS, 7001, Australia., McMahon C; Faculty of Medicine and Health Sciences, The Hearing Hub, Macquarie University, Sydney, 2109, Australia., McAlpine D; Faculty of Medicine and Health Sciences, The Hearing Hub, Macquarie University, Sydney, 2109, Australia., Birman CS; Faculty of Medicine and Health Sciences, The Hearing Hub, Macquarie University, Sydney, 2109, Australia.; Faculty of Medicine and Health, University of Sydney, Sydney, NSW, 2006, Australia.; Department of Otolaryngology, Royal Prince Alfred Hospital, Camperdown, NSW, 2050, Australia.; NextSense, Royal Institute of Deaf and Blind Children, Gladesville, NSW, 2111, Australia., Lai W; NextSense, Royal Institute of Deaf and Blind Children, Gladesville, NSW, 2111, Australia., Enke YL; Cochlear Limited, Macquarie University, University Avenue, Macquarie Park, NSW, 2109, Australia., Carter PM; Cochlear Limited, Macquarie University, University Avenue, Macquarie Park, NSW, 2109, Australia., Patrick JF; Cochlear Limited, Macquarie University, University Avenue, Macquarie Park, NSW, 2109, Australia., Gay RD; Cochlear Limited, Macquarie University, University Avenue, Macquarie Park, NSW, 2109, Australia., Marie C; CNRS, Inserm, UTCBS, Université Paris Cité, Paris, F-75006, France.; Chimie ParisTech, Université PSL, Paris, 75005, France., Scherman D; CNRS, Inserm, UTCBS, Université Paris Cité, Paris, F-75006, France.; Fondation Maladies Rares, 96 rue Didot, Paris, 75014, France., Lovell NH; Translational Neuroscience Facility, Department of Physiology, School of Biomedical Sciences, Graduate School of Biomedical Engineering, Tyree Institute for Health Engineering (IHealthE), UNSW, Sydney, NSW, 2052, Australia., Housley GD; Translational Neuroscience Facility, Department of Physiology, School of Biomedical Sciences, Graduate School of Biomedical Engineering, Tyree Institute for Health Engineering (IHealthE), UNSW, Sydney, NSW, 2052, Australia.
Jazyk: angličtina
Zdroj: Advanced science (Weinheim, Baden-Wurttemberg, Germany) [Adv Sci (Weinh)] 2024 Aug; Vol. 11 (30), pp. e2401392. Date of Electronic Publication: 2024 Jun 14.
DOI: 10.1002/advs.202401392
Abstrakt: Viral vectors and lipofection-based gene therapies have dispersion-dependent transduction/transfection profiles that thwart precise targeting. The study describes the development of focused close-field gene electrotransfer (GET) technology, refining spatial control of gene expression. Integration of fluidics for precise delivery of "naked" plasmid deoxyribonucleic acid (DNA) in sucrose carrier within the focused electric field enables negative biasing of near-field conductivity ("conductivity-clamping"-CC), increasing the efficiency of plasma membrane molecular translocation. This enables titratable gene delivery with unprecedently low charge transfer. The clinic-ready bionics-derived CC-GET device achieved neurotrophin-encoding miniplasmid DNA delivery to the cochlea to promote auditory nerve regeneration; validated in deafened guinea pig and cat models, leading to improved central auditory tuning with bionics-based hearing. The performance of CC-GET is evaluated in the brain, an organ problematic for pulsed electric field-based plasmid DNA delivery, due to high required currents causing Joule-heating and damaging electroporation. Here CC-GET enables safe precision targeting of gene expression. In the guinea pig, reporter expression is enabled in physiologically critical brainstem regions, and in the striatum (globus pallidus region) delivery of a red-shifted channelrhodopsin and a genetically-encoded Ca 2+  sensor, achieved photoactivated neuromodulation relevant to the treatment of Parkinson's Disease and other focal brain disorders.
(© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)
Databáze: MEDLINE
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