Optimizing synthetic nucleic acid and protein nanocarriers: The chemical evolution approach.
CRISPR Cas9
DNA
Intracellular delivery
Polymer
Transfection
mRNA
siRNA
Journal
Advanced drug delivery reviews
ISSN: 1872-8294
Titre abrégé: Adv Drug Deliv Rev
Pays: Netherlands
ID NLM: 8710523
Informations de publication
Date de publication:
01 2021
01 2021
Historique:
received:
22
11
2019
revised:
10
02
2020
accepted:
30
03
2020
pubmed:
5
4
2020
medline:
1
10
2021
entrez:
5
4
2020
Statut:
ppublish
Résumé
Optimizing synthetic nanocarriers is like searching for a needle in a haystack. How to find the most suitable carrier for intracellular delivery of a specified macromolecular nanoagent for a given disease target location? Here, we review different synthetic 'chemical evolution' strategies that have been pursued. Libraries of nanocarriers have been generated either by unbiased combinatorial chemistry or by variation and novel combination of known functional delivery elements. As in natural evolution, definition of nanocarriers as sequences, as barcode or design principle, may fuel chemical evolution. Screening in appropriate test system may not only provide delivery candidates, but also a refined understanding of cellular delivery including novel, unpredictable mechanisms. Combined with rational design and computational algorithms, candidates can be further optimized in subsequent evolution cycles into nanocarriers with improved safety and efficacy. Optimization of nanocarriers differs for various cargos, as illustrated for plasmid DNA, siRNA, mRNA, proteins, or genome-editing nucleases.
Identifiants
pubmed: 32246984
pii: S0169-409X(20)30019-3
doi: 10.1016/j.addr.2020.03.005
pii:
doi:
Substances chimiques
Drug Carriers
0
Macromolecular Substances
0
Nucleic Acids
0
Polymers
0
Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
30-54Informations de copyright
Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.