Resveratrol enhances mrna and sirna lipid nanoparticles primary CLL cell transfection

Edo Kon, Inbal Hazan-Halevy, Daniel Rosenblum, Niv Cohen, Sushmita Chatterjee, Nuphar Veiga, Pia Raanani, Osnat Bairey, Ohad Benjamini, Arnon Nagler, Dan Peer

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

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 therapeutics for CLL patients and advocates the use of resveratrol in combination with RNA lipid nanoparticles to enhance delivery into CLL cells.

Original languageEnglish (US)
Article number520
Pages (from-to)1-14
Number of pages14
JournalPharmaceutics
Volume12
Issue number6
DOIs
StatePublished - Jun 2020

Keywords

  • B lymphocyte
  • Caffeic acid
  • Clinic
  • Curcumin
  • Drug delivery
  • Endosomal escape
  • RNA therapies

ASJC Scopus subject areas

  • Pharmaceutical Science

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