Unknown

Dataset Information

0

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


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 using pH-sensitive labels that VIPER particles experience less acidic environments compared to control polyplexes. In summary, VIPER/siRNA polyplexes efficiently deliver siRNA in vivo resulting in robust gene silencing (>75% knockdown) within the lung.

SUBMITTER: Feldmann DP 

PROVIDER: S-EPMC6031299 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

altmetric image

Publications

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

Feldmann Daniel P DP   Cheng Yilong Y   Kandil Rima R   Xie Yuran Y   Mohammadi Mariam M   Harz Hartmann H   Sharma Akhil A   Peeler David J DJ   Moszczynska Anna A   Leonhardt Heinrich H   Pun Suzie H SH   Merkel Olivia M OM  

Journal of controlled release : official journal of the Controlled Release Society 20180220


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  ...[more]

Similar Datasets

| S-EPMC2830889 | biostudies-literature
| S-EPMC3412491 | biostudies-literature
| S-EPMC3759511 | biostudies-literature
| S-EPMC3255578 | biostudies-literature
| S-EPMC3955097 | biostudies-literature
| S-EPMC6028351 | biostudies-literature
| S-EPMC4825876 | biostudies-literature
| S-EPMC5034564 | biostudies-literature
| S-EPMC3677313 | biostudies-literature
| S-EPMC4191406 | biostudies-literature