1. An Unexpected Role of Hyaluronic Acid in Trafficking siRNA Across the Cellular Barrier: The First Biomimetic, Anionic, Non‐Viral Transfection Method
- Author
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Gaurav Mohanty, Maruthibabu Paidikondala, Ganesh N. Nawale, Turkka Salminen, Sandeep Kadekar, Vignesh K. Rangasami, Giuseppe Perale, Oommen P. Varghese, Tommaso Casalini, Oommen P. Oommen, Tampere University, BioMediTech, Research group: Biomaterials and Tissue Engineering Group, Materials Science and Environmental Engineering, Research group: Materials Characterization, Research group: Nanophotonics, and Physics
- Subjects
Anions ,Models, Molecular ,Small interfering RNA ,Cell ,010402 general chemistry ,01 natural sciences ,Non viral transfection ,Catalysis ,Extracellular matrix ,chemistry.chemical_compound ,Biomimetic Materials ,RNA interference ,Cell Line, Tumor ,Hyaluronic acid ,medicine ,Humans ,Hyaluronic Acid ,RNA, Small Interfering ,010405 organic chemistry ,Chemistry ,217 Medical engineering ,General Medicine ,General Chemistry ,Transfection ,0104 chemical sciences ,Cell biology ,medicine.anatomical_structure ,Nucleic acid - Abstract
Circulating nucleic acids, such as short interfering RNA (siRNA), regulate many biological processes; however, the mechanism by which these molecules enter the cell is poorly understood. The role of extracellular‐matrix‐derived polymers in binding siRNAs and trafficking them across the plasma membrane is reported. Thermal melting, dynamic light scattering, scanning electron microscopy, and computational analysis indicate that hyaluronic acid can stabilize siRNA via hydrogen bonding and Van der Waals interactions. This stabilization facilitated HA size‐ and concentration‐dependent gene silencing in a CD44‐positive human osteosarcoma cell line (MG‐63) and in human mesenchymal stromal cells (hMSCs). This native HA‐based siRNA transfection represents the first report on an anionic, non‐viral delivery method that resulted in approximately 60 % gene knockdown in both cell types tested, which correlated with a reduction in translation levels. acceptedVersion
- Published
- 2019
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