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Unexpected role of hyaluronic acid in trafficking siRNA across cellular barrier: First biomimetic, anionic, non-viral transfection method

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Unexpected role of hyaluronic acid in trafficking siRNA across cellular barrier: First biomimetic, anionic, non-viral transfection method. / Podiyan Oommen, Oommen; Rangasami, Vigneshkumar; Mohanty, Gaurav; Salminen, Turkka.

In: Angewandte Chemie (International Edition), Vol. 58, No. 9, 25.02.2019, p. 2815-2819.

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@article{05b34a2c1996443dbb554653ec4f9dad,
title = "Unexpected role of hyaluronic acid in trafficking siRNA across cellular barrier: First biomimetic, anionic, non-viral transfection method",
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.",
author = "{Podiyan Oommen}, Oommen and Vigneshkumar Rangasami and Gaurav Mohanty and Turkka Salminen",
year = "2019",
month = "2",
day = "25",
doi = "10.1002/anie.201900099",
language = "English",
volume = "58",
pages = "2815--2819",
journal = "Angewandte Chemie (International Edition)",
issn = "1433-7851",
publisher = "Wiley-VCH Verlag",
number = "9",

}

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TY - JOUR

T1 - Unexpected role of hyaluronic acid in trafficking siRNA across cellular barrier: First biomimetic, anionic, non-viral transfection method

AU - Podiyan Oommen, Oommen

AU - Rangasami, Vigneshkumar

AU - Mohanty, Gaurav

AU - Salminen, Turkka

PY - 2019/2/25

Y1 - 2019/2/25

N2 - 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.

AB - 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.

U2 - 10.1002/anie.201900099

DO - 10.1002/anie.201900099

M3 - Article

VL - 58

SP - 2815

EP - 2819

JO - Angewandte Chemie (International Edition)

JF - Angewandte Chemie (International Edition)

SN - 1433-7851

IS - 9

ER -