Optimizing synthetic nucleic acid and protein nanocarriers: The chemical evolution approach

Freitag, Franziska und Wagner, Ernst (2021): Optimizing synthetic nucleic acid and protein nanocarriers: The chemical evolution approach. In: Advanced Drug Delivery Reviews, Bd. 168: S. 30-54

Abstract

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. (c) 2020 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/).

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Chemie und Pharmazie > Department für Pharmazie - Zentrum für Pharmaforschung
• Themengebiete: 500 Naturwissenschaften und Mathematik > 540 Chemie
• ISSN: 0169-409X
• Sprache: Englisch