Neurotrophin gene augmentation by electrotransfer to improve cochlear implant hearing outcomes

Autor: Jeremy L. Pinyon, Daniel Scherman, David McAlpine, Andrew K. Wise, Waikong Lai, Matthias Klugmann, James F. Patrick, Edward N. Crawford, Amr Al Abed, Corinne Marie, Paul Carter, Ya Lang Enke, Gary D. Housley, Robert K. Shepherd, Anne G M Schilder, Catherine M. McMahon, Georg von Jonquieres, Nigel H. Lovell, James B Fallon, Mayryl Duxbury, Catherine S. Birman
Přispěvatelé: UNSW Faculty of Medicine [Sydney], University of New South Wales [Sydney] (UNSW), Graduate School of Biomedical Engineering, University of Melbourne, Royal Prince Alfred Hospital [Sydney, Australia], Macquarie University [Sydney], University College of London [London] (UCL), Unité de Technologies Chimiques et Biologiques pour la Santé (UTCBS - UM 4 (UMR 8258 / U1022)), Institut de Chimie du CNRS (INC)-Université de Paris (UP)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Jazyk: angličtina
Rok vydání: 2019
Předmět:
0301 basic medicine
EXPRESSION
[SDV.BIO]Life Sciences [q-bio]/Biotechnology
SPIRAL GANGLION NEURONS
medicine.medical_treatment
Gene electrotransfer
Biology
Gene delivery
THERAPY
Neural recruitment
03 medical and health sciences
DELIVERY
0302 clinical medicine
Hearing
Cochlear implant
medicine
otorhinolaryngologic diseases
Animals
Humans
Inner ear
Nerve Growth Factors
[SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs
Hearing Loss
HAIR-CELLS
Spiral ganglion
INTRACOCHLEAR ELECTRICAL-STIMULATION
Electroporation
INNER-EAR
Gene Transfer Techniques
Genetic Therapy
Recovery of Function
MOUSE MODEL
Cochlear Implantation
Combined Modality Therapy
Sensory Systems
Up-Regulation
Cell biology
Cochlear Implants
Persons With Hearing Impairments
Treatment Outcome
030104 developmental biology
medicine.anatomical_structure
WORD RECOGNITION
Auditory Perception
SURVIVAL
sense organs
Neuron death
030217 neurology & neurosurgery
Zdroj: Hearing Research
Hearing Research, Elsevier, 2019, 380, pp.137-149. ⟨10.1016/j.heares.2019.06.002⟩
ISSN: 0378-5955
DOI: 10.1016/j.heares.2019.06.002⟩
Popis: International audience; This Review outlines the development of DNA-based therapeutics for treatment of hearing loss, and in particular, considers the potential to utilize the properties of recombinant neurotrophins to improve cochlear auditory (spiral ganglion) neuron survival and repair. This potential to reduce spiral ganglion neuron death and indeed re-grow the auditory nerve fibres has been the subject of considerable preclinical evaluation over decades with the view of improving the neural interface with cochlear implants. This provides the context for discussion about the development of a novel means of using cochlear implant electrode arrays for gene electrotransfer. Mesenchymal cells which line the cochlear perilymphatic compartment can be selectively transfected with (naked) plasmid DNA using array - based gene electrotransfer, termed 'close-field electroporation'. This technology is able to drive expression of brain derived neurotrophic factor (BDNF) in the deafened guinea pig model, causing re-growth of the spiral ganglion peripheral neurites towards the mesenchymla cells, and hence into close proximity with cochlear implant electrodes within scala tympani. This was associated with functional enhancement of the cochlear implant neural interface (lower neural recruitment thresholds and expanded dynamic range, measured using electrically - evoked auditory brainstem responses). The basis for the efficiency of close-field electroporation arises from the compression of the electric field in proximity to the ganged cochlear implant electrodes. The regions close to the array with highest field strength corresponded closely to the distribution of bioreporter cells (adherent human embryonic kidney (HEK293)) expressing green fluorescent reporter protein (GFP) following gene electrotransfer. The optimization of the gene electrotransfer parameters using this cell-based model correlated closely with in vitro and in vivo cochlear gene delivery outcomes. The migration of the cochlear implant electrode array-based gene electrotransfer platform towards a clinical trial for neurotrophin-based enhancement of cochlear implants is supported by availability of a novel regulatory compliant mini-plasmid DNA backbone (pFAR4; plasmid Free of Antibiotic Resistance v.4) which could be used to package a 'humanized' neurotrophin expression cassette. A reporter cassette packaged into pFAR4 produced prominent GFP expression in the guinea pig basal turn perilymphatic scalae. More broadly, close-field gene electrotransfer may lend itself to a spectrum of potential DNA therapeutics applications benefitting from titratable, localised, delivery of naked DNA, for gene augmentation, targeted gene regulation, or gene substitution strategies. (C) 2019 Elsevier B.V. All rights reserved.
Databáze: OpenAIRE
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