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Molecules 2018, 23(7), 1586;

The Mechanism for siRNA Transmembrane Assisted by PMAL

Department of Chemical Engineering, Tsinghua University, Beijing 100084, China
Author to whom correspondence should be addressed.
Received: 16 May 2018 / Revised: 10 June 2018 / Accepted: 19 June 2018 / Published: 29 June 2018
(This article belongs to the Special Issue Directed Drug Design and Molecular Therapy)
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The capacity of silencing genes makes small interfering RNA (siRNA) appealing for curing fatal diseases. However, the naked siRNA is vulnerable to and degraded by endogenous enzymes and is too large and too negatively charged to cross cellular membranes. An effective siRNA carrier, PMAL (poly(maleic anhydride-alt-1-decene) substituted with 3-(dimethylamino) propylamine), has been demonstrated to be able to assist siRNA transmembrane by both experiments and molecular simulation. In the present work, the mechanism of siRNA transmembrane assisted by PMAL was studied using steered molecular dynamics simulations based on the martini coarse-grained model. Here two pulling rates, i.e., 10−6 and 10−5 nm·ps−1, were chosen to imitate the passive and active transport of siRNA, respectively. Potential of mean force (PMF) and interactions among siRNA, PMAL, and lipid bilayer membrane were calculated to describe the energy change during siRNA transmembrane processes at various conditions. It is shown that PMAL-assisted siRNA delivery is in the mode of passive transport. The PMAL can help siRNA insert into lipid bilayer membrane by lowering the energy barrier caused by siRNA and lipid bilayer membrane. PMAL prefers to remain in the lipid bilayer membrane and release siRNA. The above simulations establish a molecular insight of the interaction between siRNA and PMAL and are helpful for the design and applications of new carriers for siRNA delivery. View Full-Text
Keywords: siRNA; PMAL; steered molecular dynamics simulation; PMF; transmembrane delivery siRNA; PMAL; steered molecular dynamics simulation; PMF; transmembrane delivery

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Lu, Y.; Li, J.; Su, N.; Lu, D. The Mechanism for siRNA Transmembrane Assisted by PMAL. Molecules 2018, 23, 1586.

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