Dual AAV-based PCDH15 gene therapy achieves sustained rescue of visual function in a mouse model of Usher syndrome 1F.

PCDH15 USH1F arrestin dual-AAV photoreceptors protocadherin-15 retinitis pigmentosa retinoid oxime transducin

Journal

Molecular therapy : the journal of the American Society of Gene Therapy
ISSN: 1525-0024
Titre abrégé: Mol Ther
Pays: United States
ID NLM: 100890581

Informations de publication

Date de publication:
06 Dec 2023
Historique:
received: 15 06 2023
revised: 20 09 2023
accepted: 18 10 2023
pubmed: 21 10 2023
medline: 21 10 2023
entrez: 21 10 2023
Statut: ppublish

Résumé

Mutations in the PCDH15 gene, encoding protocadherin-15, are among the leading causes of Usher syndrome type 1 (USH1F), and account for up to 12% USH1 cases worldwide. A founder truncating variant of PCDH15 has a ∼2% carrier frequency in Ashkenazi Jews accounting for nearly 60% of their USH1 cases. Although cochlear implants can restore hearing perception in USH1 patients, presently there are no effective treatments for the vision loss due to retinitis pigmentosa. We established a founder allele-specific Pcdh15 knockin mouse model as a platform to ascertain therapeutic strategies. Using a dual-vector approach to circumvent the size limitation of adeno-associated virus, we observed robust expression of exogenous PCDH15 in the retinae of Pcdh15

Identifiants

DOI: 10.1016/j.ymthe.2023.10.017 PMID: 37864333
pubmed: 37864333
pii: S1525-0016(23)00558-0
doi: 10.1016/j.ymthe.2023.10.017
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

3490-3501

Informations de copyright

Copyright © 2023. Published by Elsevier Inc.

Déclaration de conflit d'intérêts

Declaration of interests S.S., L.S.C., Saima Riazuddin, and Z.M.A. filed a patent application for the composition of a protocadherin-15 dual vector system.

Auteurs

Sehar Riaz (S)

Department of Otorhinolaryngology - Head & Neck Surgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA; National Centre of Excellence in Molecular Biology, University of the Punjab, Lahore 54500, Pakistan.

Saumil Sethna (S)

Department of Otorhinolaryngology - Head & Neck Surgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA.

Todd Duncan (T)

Laboratory of Retinal Cell and Molecular Biology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA.

Muhammad A Naeem (MA)

National Centre of Excellence in Molecular Biology, University of the Punjab, Lahore 54500, Pakistan.

T Michael Redmond (TM)

Laboratory of Retinal Cell and Molecular Biology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA.

Sheikh Riazuddin (S)

Jinnah Burn and Reconstructive Surgery Centre, Allama Iqbal Medical Research, University of Health Sciences, Lahore 54500, Pakistan.

Saima Riazuddin (S)

Department of Otorhinolaryngology - Head & Neck Surgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA; Department of Molecular Biology and Biochemistry, University of Maryland School of Medicine, Baltimore, MD 21201, USA.

Livia S Carvalho (LS)

Centre for Ophthalmology and Visual Science, The University of Western Australia, Crawley, WA 6009, Australia; Retinal Genomics and Therapy Group, Lions Eye Institute Ltd, Nedlands, WA 6009, Australia.

Zubair M Ahmed (ZM)

Department of Otorhinolaryngology - Head & Neck Surgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA; Department of Molecular Biology and Biochemistry, University of Maryland School of Medicine, Baltimore, MD 21201, USA; Department of Ophthalmology and Visual Sciences, University of Maryland School of Medicine, Baltimore, MD 21201, USA. Electronic address: zmahmed@som.umaryland.edu.

Classifications MeSH