Analyzing efficacy, stability, and safety of AAV-mediated optogenetic hearing restoration in mice.
Journal
Life science alliance
ISSN: 2575-1077
Titre abrégé: Life Sci Alliance
Pays: United States
ID NLM: 101728869
Informations de publication
Date de publication:
08 2022
08 2022
Historique:
received:
14
12
2021
revised:
11
04
2022
accepted:
12
04
2022
entrez:
5
5
2022
pubmed:
6
5
2022
medline:
10
5
2022
Statut:
epublish
Résumé
AAV-mediated optogenetic neural stimulation has become a clinical approach for restoring function in sensory disorders and feasibility for hearing restoration has been indicated in rodents. Nonetheless, long-term stability and safety of AAV-mediated channelrhodopsin (ChR) expression in spiral ganglion neurons (SGNs) remained to be addressed. Here, we used longitudinal studies on mice subjected to early postnatal administration of AAV2/6 carrying fast gating ChR f-Chrimson under the control of the human synapsin promoter unilaterally to the cochlea. f-Chrimson expression in SGNs in both ears and the brain was probed in animals aged 1 mo to 2 yr. f-Chrimson was observed in SGNs at all ages indicating longevity of ChR-expression. SGN numbers in the AAV-injected cochleae declined with age faster than in controls. Investigations were extended to the brain in which viral transduction was observed across the organ at varying degrees irrespective of age without observing viral spread-related pathologies. No viral DNA or virus-related histopathological findings in visceral organs were encountered. In summary, our study demonstrates life-long (24 mo in mice) expression of f-Chrimson in SGNs upon single AAV-dosing of the cochlea.
Identifiants
pubmed: 35512833
pii: 5/8/e202101338
doi: 10.26508/lsa.202101338
pmc: PMC9258265
pii:
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : European Research Council
ID : 670759
Pays : International
Informations de copyright
© 2022 Bali et al.
Références
Annu Rev Neurosci. 2013 Jul 8;36:467-88
pubmed: 23724995
Best Pract Res Clin Endocrinol Metab. 2004 Sep;18(3):407-21
pubmed: 15261846
EMBO Mol Med. 2020 Apr 7;12(4):e11618
pubmed: 32227585
Nat Commun. 2018 Sep 12;9(1):3691
pubmed: 30209249
Elife. 2020 Jan 08;9:
pubmed: 31913118
Nat Genet. 2001 Feb;27(2):143-9
pubmed: 11175778
EMBO Mol Med. 2019 Jan;11(1):
pubmed: 30509897
Annu Rev Virol. 2019 Sep 29;6(1):601-621
pubmed: 31283441
Sci Transl Med. 2020 Jul 22;12(553):
pubmed: 32718992
PLoS One. 2011;6(11):e27520
pubmed: 22114676
Hear Res. 2012 Jan;283(1-2):80-8
pubmed: 22138310
Nat Rev Neurol. 2016 Mar;12(3):135-49
pubmed: 26891769
Mol Ther. 2000 Oct;2(4):368-73
pubmed: 11020352
Nat Commun. 2018 May 1;9(1):1750
pubmed: 29717130
Vet Pathol. 2013 Nov;50(6):1007-15
pubmed: 23558974
Front Mol Neurosci. 2021 Jan 07;13:600051
pubmed: 33488357
Pharmacol Ther. 2020 Mar;207:107453
pubmed: 31836454
EMBO J. 2015 Nov 3;34(21):2686-702
pubmed: 26446278
Acta Otolaryngol. 1974 May;77(5):327-34
pubmed: 4835632
Elife. 2021 Jul 14;10:
pubmed: 34259630
Nat Med. 2021 Jul;27(7):1223-1229
pubmed: 34031601
J Clin Invest. 2014 Mar;124(3):1114-29
pubmed: 24509078
Nat Commun. 2019 Apr 29;10(1):1962
pubmed: 31036812
Hear Res. 2015 Apr;322:224-34
pubmed: 25601298
Front Mol Neurosci. 2021 Mar 11;14:635897
pubmed: 33776648
Physiol Rev. 2020 Oct 1;100(4):1467-1525
pubmed: 32191560
JCI Insight. 2019 Aug 8;4(15):
pubmed: 31391336
Brain Behav Immun. 2016 May;54:211-225
pubmed: 26872418
Nat Commun. 2019 Jan 24;10(1):409
pubmed: 30679421
Nat Biotechnol. 2017 Mar;35(3):280-284
pubmed: 28165475
Network. 2016;27(2-3):212-236
pubmed: 27644125
Nat Neurosci. 2005 Sep;8(9):1263-8
pubmed: 16116447
J Neural Eng. 2020 Nov 04;17(5):056046
pubmed: 33036009
Cell. 2018 Aug 23;174(5):1229-1246.e17
pubmed: 30078709
Annu Rev Genet. 2001;35:589-646
pubmed: 11700295
J Neurosci. 2013 Aug 21;33(34):13686-94
pubmed: 23966690
Proc Natl Acad Sci U S A. 2009 Nov 17;106(46):19432-7
pubmed: 19901338
Gene Ther. 1996 Jul;3(7):588-92
pubmed: 8818645
Neuron. 2012 Jul 26;75(2):283-93
pubmed: 22841313
PLoS One. 2014 Mar 17;9(3):e92133
pubmed: 24637518
Front Cell Neurosci. 2019 Oct 30;13:471
pubmed: 31736710
Mol Ther. 2018 Aug 1;26(8):1931-1939
pubmed: 30017876
EMBO J. 2018 Dec 14;37(24):
pubmed: 30396994
Sci Transl Med. 2015 Jul 8;7(295):295ra108
pubmed: 26157030
Commun Biol. 2021 Jan 27;4(1):125
pubmed: 33504896
Sci Transl Med. 2018 Jul 11;10(449):
pubmed: 29997248
EMBO Mol Med. 2020 Aug 7;12(8):e12387
pubmed: 32596983
Cell. 2018 Aug 23;174(5):1247-1263.e15
pubmed: 30078710
EMBO Mol Med. 2021 Jun 7;13(6):e13391
pubmed: 33960685
Gene Ther. 2016 Feb;23(2):158-66
pubmed: 26440056