Charge-altering releasable transporters enhance mRNA delivery in vitro and exhibit in vivo tropism

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 oligome...

Celý popis

Uloženo v:
Podrobná bibliografie
Vydáno v:Nature communications Ročník 14; číslo 1; s. 6983 - 15
Hlavní autoři: Li, Zhijian, Amaya, Laura, Pi, Ruoxi, Wang, Sean K., Ranjan, Alok, Waymouth, Robert M., Blish, Catherine A., Chang, Howard Y., Wender, Paul A.
Médium: Journal Article
Jazyk:angličtina
Vydáno: London Nature Publishing Group UK 01.11.2023
Nature Publishing Group
Nature Portfolio
Témata:
13/1
13/106
13/109
13/21
13/31
140/131
140/58
59
59/5
631/61/54/152
639/638/298/54/152
639/638/455/941
64
64/60
Biomedical materials
Cancer vaccines
Carts
Gene Editing
Genome editing
Genomes
Humanities and Social Sciences
Immunotherapy
Lipids
Lymphocytes
Lymphocytes T
mRNA
multidisciplinary
Polymers
Protein expression
Proteins
RNA, Messenger - metabolism
Science
Science (multidisciplinary)
System effectiveness
T-Lymphocytes - metabolism
Transfection
Tropism
ISSN:2041-1723, 2041-1723
On-line přístup:Získat plný text
Tagy: Přidat tag
Žádné tagy, Buďte první, kdo vytvoří štítek k tomuto záznamu!
Popis
Shrnutí: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. Polymers are promising for mRNA delivery, but can have limited efficacy in hard to transfect cells. Here, the authors report charge-altering releasable transporters for improved mRNA transfection in primary T-lymphocytes and enhanced and selective protein expression in vivo.
Bibliografie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 14
content type line 23
ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-023-42672-x