Tackling the Limitations of Copolymeric Small Interfering RNA Delivery Agents by a Combined Experimental–Computational Approach
| Autor: | Maziar Heidari, Raffaello Potestio, Kerstin Nagel-Wolfrum, Kaloian Koynov, Christoph Freidel, Philip Biehl, Ilja Tabujew, Lars Tebbe, Kalina Peneva, Uwe Wolfrum, Mark Helm, Felix H. Schacher |
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| Rok vydání: | 2019 |
| Předmět: |
Small interfering RNA
Polymers and Plastics Bioengineering 02 engineering and technology Computational biology Biology 010402 general chemistry 01 natural sciences Virus Biomaterials Drug Delivery Systems Text mining Materials Chemistry Humans Computer Simulation RNA Small Interfering business.industry RNA 021001 nanoscience & nanotechnology 0104 chemical sciences HEK293 Cells Models Chemical MCF-7 Cells 0210 nano-technology business HeLa Cells |
| Zdroj: | Biomacromolecules. 20:4389-4406 |
| ISSN: | 1526-4602 1525-7797 |
| DOI: | 10.1021/acs.biomac.9b01061 |
| Popis: | Despite the first successful applications of nonviral delivery vectors for small interfering RNA in the treatment of illnesses, such as the respiratory syncytial virus infection, the preparation of a clinically suitable, safe, and efficient delivery system still remains a challenge. In this study, we tackle the drawbacks of the existing systems by a combined experimental-computational in-depth investigation of the influence of the polymer architecture over the binding and transfection efficiency. For that purpose, a library of diblock copolymers with a molar mass of 30 kDa and a narrow dispersity (Đ1.12) was synthesized. We studied in detail the impact of an altered block size and/or composition of cationic diblock copolymers on the viability of each respective structure as a delivery agent for polynucleotides. The experimental investigation was further complemented by a computational study employing molecular simulations as well as an analytical description of systemic properties. This is the first report in which molecular dynamics simulations of RNA/cationic polymer complexes have been performed. Specifically, we developed and employed a coarse-grained model of the system at the molecular level to study the interactions between polymer chains and small interfering RNA. We were further able to confirm a threshold length |
| Databáze: | OpenAIRE |
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