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Drug Des Devel Ther. 2019 Apr 4;13:1059-1068. doi: 10.2147/DDDT.S195481. eCollection 2019.
Transportan-derived cell-penetrating peptide delivers siRNA to inhibit replication of influenza virus in vivo.
Zhang C1, Ren W1, Liu Q2, Tan Z3, Li J1, Tong C3.
Author information
Abstract
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:
CPP; IV; NP; cell-penetrating peptide; influenza virus; inhibition; nucleoprotein; siRNA; transportan
PMID: 31040643 PMCID: PMC6454991 DOI: 10.2147/DDDT.S195481
Transportan-derived cell-penetrating peptide delivers siRNA to inhibit replication of influenza virus in vivo.
Zhang C1, Ren W1, Liu Q2, Tan Z3, Li J1, Tong C3.
Author information
Abstract
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:
CPP; IV; NP; cell-penetrating peptide; influenza virus; inhibition; nucleoprotein; siRNA; transportan
PMID: 31040643 PMCID: PMC6454991 DOI: 10.2147/DDDT.S195481