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Transportan-derived cell-penetrating peptide delivers siRNA to inhibit replication of influenza virus in vivo

Authors Zhang C, Ren W, Liu Q, Tan Z, Li J, Tong C

Received 21 November 2018

Accepted for publication 16 February 2019

Published 4 April 2019 Volume 2019:13 Pages 1059—1068

DOI https://doi.org/10.2147/DDDT.S195481

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Colin Mak

Peer reviewer comments 2

Editor who approved publication: Prof. Dr. Cristiana Tanase


Cuiling Zhang,1 Weigang Ren,1 Qingxin Liu,2 Zhikai Tan,3 Junwei Li,1 Chunyi Tong3

1College of Veterinary Medicine, Qingdao Agricultural University, Qingdao 266109, People’s Republic of China; 2Jiangsu Vocational College of Agriculture and Forestry, Jurong 212400, People’s Republic of China; 3Hunan Province Key Laboratory of Plant Functional Genomics and Developmental Regulation, State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Biology, Hunan University, Changsha 410082, People’s Republic of China

Introduction: In this study, we report on the development of an effective delivery system for siRNAs; a novel cell-penetrating peptide (CPP), T9(dR), obtained from transportan (TP), was used for in vivo and in vitro testing.
Methods: In this study, toxicity of T9(dR) and TP and efficient delivery of siRNA were tested in 293T, MDCK, RAW, and A549 cells. Furthermore, T9(dR)- and TP-delivered siRNAs against nucleoprotein (NP) gene segment of influenza virus (siNP) were studied in both cell lines and mice.
Results: Gel retardation showed that T9(dR) effectively condensed siRNA into nanoparticles sized between 350 and 550 nm when the mole ratio of T9(dR) to siRNA was ≥4:1. In vitro studies demonstrated that T9(dR) successfully delivered siRNA with low cellular toxicity into several cell lines. It was also observed that T9(dR)-delivered siRNAs inhibited replication of influenza virus more efficiently as compared to that delivered by TP into the MDCK and A549 cells. It was also noticed that when given a combined tail vein injection of siNP and T9(dR) or TP, all mice in the 50 nmol siNP group infected with PR8 influenza virus survived and showed weight recovery at 2 weeks post-infection.
Conclusion: This study indicates that T9(dR) is a promising siRNA delivery tool with potential application for nucleotide drug delivery.

Keywords: cell-penetrating peptide, CPP, siRNA, inhibition, influenza virus, IV, transportan, nucleoprotein, NP

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