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The impact of heparin and direct thrombin inhibitors on cell-penetrating polymer siRNA transfection.

Authors :
Mota L
Zhu M
Tomeo JN
Recarey M
Patel N
Pradhan-Nabzdyk L
LoGerfo FW
Liang P
Source :
Gene therapy [Gene Ther] 2024 Sep; Vol. 31 (9-10), pp. 467-476. Date of Electronic Publication: 2024 Jul 16.
Publication Year :
2024

Abstract

Gene therapy using siRNA has become a promising strategy to achieve targeted gene knockdown for treatment of cardiovascular pathologies. However, efficient siRNA transfection often relies on cationic delivery vectors such as synthetic cell-penetrating polymers which are susceptible to interference by negatively charged molecules. Anticoagulants such as heparin, which is negatively charged and widely used in cardiovascular applications, may pose a significant barrier to effective siRNA delivery. We therefore conducted in vitro studies utilizing human smooth muscle and endothelial cells transfected with glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and β <subscript>2</subscript> -microglobulin (B2M) siRNA in the presence of heparin, argatroban, and bivalirudin in order to determine which anticoagulant therapy is most compatible for siRNA delivery. We observed that while heparin, at clinical doses, decreases the efficiency of siRNA targeted mRNA knockdown, mRNA knockdown is not inhibited in the presence of either argatroban or bivalirudin. Our data suggests that heparin should be avoided during siRNA therapy with cationic transfection agents, and argatroban and bivalirudin should be used in its stead.<br /> (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Details

Language :
English
ISSN :
1476-5462
Volume :
31
Issue :
9-10
Database :
MEDLINE
Journal :
Gene therapy
Publication Type :
Academic Journal
Accession number :
39013986
Full Text :
https://doi.org/10.1038/s41434-024-00460-2