In vitro and in vivo delivery of siRNA via VIPER polymer system to lung cells

Journal of Controlled Release : Official Journal of the Controlled Release Society
Daniel P FeldmannOlivia M Merkel

Abstract

The block copolymer VIPER (virus-inspired polymer for endosomal release) has been reported to be a promising novel delivery system of DNA plasmids both in vitro and in vivo. VIPER is comprised of a polycation segment for condensation of nucleic acids as well as a pH-sensitive segment that exposes the membrane lytic peptide melittin in acidic environments to facilitate endosomal escape. The objective of this study was to investigate VIPER/siRNA polyplex characteristics, and compare their in vitro and in vivo performance with commercially available transfection reagents and a control version of VIPER lacking melittin. VIPER/siRNA polyplexes were formulated and characterized at various charge ratios and shown to be efficiently internalized in cultured cells. Target mRNA knockdown was confirmed by both flow cytometry and qRT-PCR and the kinetics of knockdown was monitored by live cell spinning disk microscopy, revealing knockdown starting by 4 h post-delivery. Intratracheal instillation of VIPER particles formulated with sequence specific siRNA to the lung of mice resulted in a significantly more efficient knockdown of GAPDH compared to treatment with VIPER particles formulated with scrambled sequence siRNA. We also demonstrated us...Continue Reading

Citations

Jan 12, 2019·Biomaterials Science·Brynn R OldenSuzie H Pun
Jul 11, 2019·Pharmaceutical Research·Aditi MehtaOlivia M Merkel
May 23, 2019·Therapeutic Delivery·Denish BardoliwalaAmbikanandan Misra
Apr 9, 2020·Wiley Interdisciplinary Reviews. Nanomedicine and Nanobiotechnology·Tobias W M KeilOlivia M Merkel
Sep 7, 2018·Frontiers in Pharmacology·Mikhail Durymanov, Joshua Reineke
Oct 7, 2020·Biomaterials Science·Xiaojing ChenYilong Cheng
Jan 16, 2021·Drug Discovery Today·Bilal Ahamad ParayMohammad Z Ahmed
Apr 5, 2020·Advanced Drug Delivery Reviews·Franziska Freitag, Ernst Wagner
Jan 19, 2021·Expert Opinion on Drug Delivery·Mohammad HajimolaaliFarid Dorkoosh
Nov 13, 2020·Journal of Controlled Release : Official Journal of the Controlled Release Society·Ling DingDavid Oupický
May 11, 2021·Drug Delivery and Translational Research·Indra RautelaManish Dev Sharma
Nov 7, 2018·Bioconjugate Chemistry·David J PeelerSuzie H Pun
Jan 8, 2021·ACS Applied Materials & Interfaces·Changrong WangAnjie Dong

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