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Title: Charge-altering releasable transporters enhance mRNA delivery in vitro and exhibit in vivo tropism
Abstract The introduction of more effective and selective mRNA delivery systems is required for the advancement of many emerging biomedical technologies including the development of prophylactic and therapeutic vaccines, immunotherapies for cancer and strategies for genome editing. While polymers and oligomers have served as promising mRNA delivery systems, their efficacy in hard-to-transfect cells such as primary T lymphocytes is often limited as is their cell and organ tropism. To address these problems, considerable attention has been placed on structural screening of various lipid and cation components of mRNA delivery systems. Here, we disclose a class of charge-altering releasable transporters (CARTs) that differ from previous CARTs based on their beta-amido carbonate backbone (bAC) and side chain spacing. These bAC-CARTs exhibit enhanced mRNA transfection in primary T lymphocytes in vitro and enhanced protein expression in vivo with highly selective spleen tropism, supporting their broader therapeutic use as effective polyanionic delivery systems.  more » « less
Award ID(s):
2002933
PAR ID:
10545572
Author(s) / Creator(s):
; ; ; ; ; ; ; ;
Publisher / Repository:
Nature Communications
Date Published:
Journal Name:
Nature Communications
Volume:
14
Issue:
1
ISSN:
2041-1723
Page Range / eLocation ID:
6983
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
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