In utero adeno-associated virus (AAV)-mediated gene delivery targeting sensory and supporting cells in the embryonic mouse inner ear.

Autor: Barbosa Spinola CM; Université Paris Cité, Institut Pasteur, AP-HP, Inserm, Fondation pour l'Audition, Institut de l'Audition, IHU reConnect, F-75012 Paris, France.; Sorbonne Université, Collège Doctoral, Paris, France., Boutet de Monvel J; Université Paris Cité, Institut Pasteur, AP-HP, Inserm, Fondation pour l'Audition, Institut de l'Audition, IHU reConnect, F-75012 Paris, France., Safieddine S; Université Paris Cité, Institut Pasteur, AP-HP, Inserm, Fondation pour l'Audition, Institut de l'Audition, IHU reConnect, F-75012 Paris, France.; Centre National de la Recherche Scientifique, Paris, France., Lahlou G; Université Paris Cité, Institut Pasteur, AP-HP, Inserm, Fondation pour l'Audition, Institut de l'Audition, IHU reConnect, F-75012 Paris, France.; APHP Sorbonne Université, Département d'Oto-Rhino-Laryngologie, Unité Fonctionnelle Implants Auditifs,Groupe Hospitalo-Universitaire Pitié-Salpêtrière, Paris, France., Etournay R; Université Paris Cité, Institut Pasteur, AP-HP, Inserm, Fondation pour l'Audition, Institut de l'Audition, IHU reConnect, F-75012 Paris, France.; Sorbonne Université, Collège Doctoral, Paris, France.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2024 Jul 19; Vol. 19 (7), pp. e0305742. Date of Electronic Publication: 2024 Jul 19 (Print Publication: 2024).
DOI: 10.1371/journal.pone.0305742
Abstrakt: In vivo gene delivery to tissues using adeno-associated vector (AAVs) has revolutionized the field of gene therapy. Yet, while sensorineural hearing loss is one of the most common sensory disorders worldwide, gene therapy applied to the human inner ear is still in its infancy. Recent advances in the development recombinant AAVs have significantly improved their cell tropism and transduction efficiency across diverse inner ear cell types to a level that renders this tool valuable for conditionally manipulating gene expression in the context of developmental biology studies of the mouse inner ear. Here, we describe a protocol for in utero micro-injection of AAVs into the embryonic inner ear, using the AAV-PHP.eB and AAV-DJ serotypes that respectively target the sensory hair cells and the supporting cells of the auditory sensory epithelium. We also aimed to standardize procedures for imaging acquisition and image analysis to foster research reproducibility and allow accurate comparisons between studies. We find that AAV-PHP.eB and AAV-DJ provide efficient and reliable tools for conditional gene expression targeting cochlear sensory and supporting cells in the mouse inner ear, from late embryonic stages on.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2024 Barbosa Spinola et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
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