cris.boxmetadata.label.title
Human MiniPromoters for ocular-rAAV expression in ON bipolar, cone, corneal, endothelial, Müller glial, and PAX6 cells
cris.boxmetadata.label.dateissued
01 browse.startsWith.months.june 2021
cris.boxmetadata.label.accesslevel
open access
cris.boxmetadata.label.resourcetype
journal article
cris.boxmetadata.label.authors
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
cris.boxmetadata.label.publisher
Springer Nature
cris.boxmetadata.label.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.
cris.boxmetadata.label.citationstartpage
351
cris.boxmetadata.label.citationendpage
372
cris.boxmetadata.label.volume
28
cris.boxmetadata.label.issue
6
cris.boxmetadata.label.language
English
cris.boxmetadata.label.ocdeknowledgeArea
Oftalmología Genética, Herencia
cris.boxmetadata.label.doi
cris.boxmetadata.label.scopusidentifier
2-s2.0-85100292496
cris.boxmetadata.label.pubmedidentifier
cris.boxmetadata.label.source
Gene Therapy
cris.boxmetadata.label.containerissn
09697128
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