Title
Human MiniPromoters for ocular-rAAV expression in ON bipolar, cone, corneal, endothelial, Müller glial, and PAX6 cells
Date Issued
01 June 2021
Access level
open access
Resource Type
journal article
Author(s)
Korecki A.J.
Fornes O.
Agostinone J.
Farkas R.A.
Hickmott J.W.
Lam S.L.
Mathelier A.
Zhou M.
Wasserman W.W.
Di Polo A.
Simpson E.M.
Universidad de Montreal
Publisher(s)
Springer Nature
Abstract
Small and cell-type restricted promoters are important tools for basic and preclinical research, and clinical delivery of gene therapies. In clinical gene therapy, ophthalmic trials have been leading the field, with over 50% of ocular clinical trials using promoters that restrict expression based on cell type. Here, 19 human DNA MiniPromoters were bioinformatically designed for rAAV, tested by neonatal intravenous delivery in mouse, and successful MiniPromoters went on to be tested by intravitreal, subretinal, intrastromal, and/or intravenous delivery in adult mouse. We present promoter development as an overview for each cell type, but only show results in detail for the recommended MiniPromoters: Ple265 and Ple341 (PCP2) ON bipolar, Ple349 (PDE6H) cone, Ple253 (PITX3) corneal stroma, Ple32 (CLDN5) endothelial cells of the blood–retina barrier, Ple316 (NR2E1) Müller glia, and Ple331 (PAX6) PAX6 positive. Overall, we present a resource of new, redesigned, and improved MiniPromoters for ocular gene therapy that range in size from 784 to 2484 bp, and from weaker, equal, or stronger in strength relative to the ubiquitous control promoter smCBA. All MiniPromoters will be useful for therapies involving small regulatory RNA and DNA, and proteins ranging from 517 to 1084 amino acids, representing 62.9–90.2% of human proteins.
Start page
351
End page
372
Volume
28
Issue
6
Language
English
OCDE Knowledge area
Genética, Herencia Oftalmología
Scopus EID
2-s2.0-85100292496
PubMed ID
Source
Gene Therapy
ISSN of the container
09697128
Sources of information: Directorio de Producción Científica Scopus