Resveratrol Enhances mRNA and siRNA Lipid Nanoparticles Primary CLL Cell Transfection

Pharmaceutics
Edo KonDan Peer

Abstract

Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in Western populations. Therapies such as mRNA and siRNA encapsulated in lipid nanoparticles (LNPs) represent a clinically advanced platform and are utilized for a wide variety of applications. Unfortunately, transfection of RNA into CLL cells remains a formidable challenge and a bottleneck for developing targeted therapies for this disease. Therefore, we aimed to elucidate the barriers to efficient transfection of RNA-encapsulated LNPs into primary CLL cells to advance therapies in the future. To this end, we transfected primary CLL patient samples with mRNA and siRNA payloads encapsulated in an FDA-approved LNP formulation and characterized the transfection. Additionally, we tested the potential of repurposing caffeic acid, curcumin and resveratrol to enhance the transfection of nucleic acids into CLL cells. The results demonstrate that the rapid uptake of LNPs is required for successful transfection. Furthermore, we demonstrate that resveratrol enhances the delivery of both mRNA and siRNA encapsulated in LNPs into primary CLL patient samples, overcoming inter-patient heterogeneity. This study points out the important challenges to consider for efficient RNA...Continue Reading

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Citations

Nov 17, 2020·Frontiers in Chemistry·Maria L GuevaraStefano Persano
Apr 20, 2021·Frontiers in Oncology·María Zenaida Saavedra-LeosMacrina Beatriz Silva-Cázares
Jul 5, 2021·International Journal of Pharmaceutics·Manon BergerGéraldine Piel

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Methods Mentioned

BETA
transfection
transfect
RNA Assay
dynamic light scattering
FCS
FACS
flow cytometry
confocal microscopy
transfections

Clinical Trials Mentioned

NCT04064905
NCT04283461

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