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Gene Electrotransfer via Conductivity-Clamped Electric Field Focusing Pivots Sensori-Motor DNA Therapeutics: "A Spoonful of Sugar Helps the Medicine Go Down".
Pinyon, Jeremy L; von Jonquieres, Georg; Crawford, Edward N; Abed, Amr Al; Power, John M; Klugmann, Matthias; Browne, Cherylea J; Housley, David M; Wise, Andrew K; Fallon, James B; Shepherd, Robert K; Lin, John Y; McMahon, Catherine; McAlpine, David; Birman, Catherine S; Lai, Waikong; Enke, Ya Lang; Carter, Paul M; Patrick, James F; Gay, Robert D; Marie, Corinne; Scherman, Daniel; Lovell, Nigel H; Housley, Gary D.
Afiliación
  • 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.
  • von Jonquieres G; Charles Perkins Centre, School of Medical Sciences, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, 2006, 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.
  • 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; Medical Sciences, School of Science, Western Sydney University, Sydney, NSW, 2560, Australia.
  • Fallon JB; 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.
  • Shepherd RK; Bionics Institute, 384-388 Albert Street, East Melbourne, VIC, 3002, Australia.
  • Lin JY; Medical Bionics, Department of Otolaryngology, University of Melbourne, Melbourne, VIC, 3002, Australia.
  • McMahon C; Bionics Institute, 384-388 Albert Street, East Melbourne, VIC, 3002, Australia.
  • McAlpine D; Medical Bionics, Department of Otolaryngology, University of Melbourne, Melbourne, VIC, 3002, Australia.
  • Birman CS; Bionics Institute, 384-388 Albert Street, East Melbourne, VIC, 3002, Australia.
  • Lai W; Medical Bionics, Department of Otolaryngology, University of Melbourne, Melbourne, VIC, 3002, Australia.
  • Enke YL; Tasmanian School of Medicine, University of Tasmania, Hobart, TAS, 7001, Australia.
  • Carter PM; Faculty of Medicine and Health Sciences, The Hearing Hub, Macquarie University, Sydney, 2109, Australia.
  • Patrick JF; Faculty of Medicine and Health Sciences, The Hearing Hub, Macquarie University, Sydney, 2109, Australia.
  • Gay RD; Faculty of Medicine and Health Sciences, The Hearing Hub, Macquarie University, Sydney, 2109, Australia.
  • Marie C; Faculty of Medicine and Health, University of Sydney, Sydney, NSW, 2006, Australia.
  • Scherman D; Department of Otolaryngology, Royal Prince Alfred Hospital, Camperdown, NSW, 2050, Australia.
  • Lovell NH; NextSense, Royal Institute of Deaf and Blind Children, Gladesville, NSW, 2111, Australia.
  • Housley GD; NextSense, Royal Institute of Deaf and Blind Children, Gladesville, NSW, 2111, Australia.
Adv Sci (Weinh) ; : e2401392, 2024 Jun 14.
Article en En | MEDLINE | ID: mdl-38874431
ABSTRACT
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 Ca2+ sensor, achieved photoactivated neuromodulation relevant to the treatment of Parkinson's Disease and other focal brain disorders.
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Texto completo: 1 Banco de datos: MEDLINE Idioma: En Año: 2024 Tipo del documento: Article
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Texto completo: 1 Banco de datos: MEDLINE Idioma: En Año: 2024 Tipo del documento: Article