Lipid nanoparticles for delivery of messenger RNA to the back of the eye.
Eye
Lipid nanoparticle
Retina
Retinal degeneration
Transfection efficiency
mRNA
Journal
Journal of controlled release : official journal of the Controlled Release Society
ISSN: 1873-4995
Titre abrégé: J Control Release
Pays: Netherlands
ID NLM: 8607908
Informations de publication
Date de publication:
10 06 2019
10 06 2019
Historique:
received:
06
03
2019
revised:
03
04
2019
accepted:
10
04
2019
pubmed:
16
4
2019
medline:
26
9
2020
entrez:
16
4
2019
Statut:
ppublish
Résumé
Retinal gene therapy has had unprecedented success in generating treatments that can halt vision loss. However, immunogenic response and long-term toxicity with the use of viral vectors remain a concern. Non-viral vectors are relatively non-immunogenic, scalable platforms that have had limited success with DNA delivery to the eye. Messenger RNA (mRNA) therapeutics has expanded the ability to achieve high gene expression while eliminating unintended genomic integration or the need to cross the restrictive nuclear barrier. Lipid-based nanoparticles (LNPs) remain at the forefront of potent delivery vectors for nucleic acids. Herein, we tested eleven different LNP variants for their ability to deliver mRNA to the back of the eye. LNPs that contained ionizable lipids with low pKa and unsaturated hydrocarbon chains showed the highest amount of reporter gene transfection in the retina. The kinetics of gene expression showed a rapid onset (within 4 h) that persisted for 96 h. The gene delivery was cell-type specific with majority of the expression in the retinal pigmented epithelium (RPE) and limited expression in the Müller glia. LNP-delivered mRNA can be used to treat monogenic retinal degenerative disorders of the RPE. The transient nature of mRNA-based therapeutics makes it desirable for applications that are directed towards retinal reprogramming or genome editing. Overall, non-viral delivery of RNA therapeutics to diverse cell types within the retina can provide transformative new approaches to prevent blindness.
Identifiants
pubmed: 30986436
pii: S0168-3659(19)30215-9
doi: 10.1016/j.jconrel.2019.04.015
pmc: PMC6579630
mid: NIHMS1527498
pii:
doi:
Substances chimiques
Lipids
0
RNA, Messenger
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
91-100Subventions
Organisme : NEI NIH HHS
ID : P30 EY010572
Pays : United States
Organisme : NIBIB NIH HHS
ID : R15 EB021581
Pays : United States
Informations de copyright
Copyright © 2019 Elsevier B.V. All rights reserved.
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