Jump to main content
Jump to site search

Issue 10, 2014
Previous Article Next Article

Organ-targeted high-throughput in vivo biologics screen identifies materials for RNA delivery

Author affiliations

Abstract

Therapies based on biologics involving delivery of proteins, DNA, and RNA are currently among the most promising approaches. However, although large combinatorial libraries of biologics and delivery vehicles can be readily synthesized, there are currently no means to rapidly characterize them in vivo using animal models. Here, we demonstrate high-throughput in vivo screening of biologics and delivery vehicles by automated delivery into target tissues of small vertebrates with developed organs. Individual zebrafish larvae are automatically oriented and immobilized within hydrogel droplets in an array format using a microfluidic system, and delivery vehicles are automatically microinjected to target organs with high repeatability and precision. We screened a library of lipid-like delivery vehicles for their ability to facilitate the expression of protein-encoding RNAs in the central nervous system. We discovered delivery vehicles that are effective in both larval zebrafish and rats. Our results showed that the in vivo zebrafish model can be significantly more predictive of both false positives and false negatives in mammals than in vitro mammalian cell culture assays. Our screening results also suggest certain structure–activity relationships, which can potentially be applied to design novel delivery vehicles.

Graphical abstract: Organ-targeted high-throughput in vivo biologics screen identifies materials for RNA delivery

Back to tab navigation

Supplementary files

Publication details

The article was received on 30 Jun 2014, accepted on 05 Aug 2014 and first published on 05 Aug 2014


Article type: Paper
DOI: 10.1039/C4IB00150H
Author version available: Download Author version (PDF)
Citation: Integr. Biol., 2014,6, 926-934
  •   Request permissions

    Organ-targeted high-throughput in vivo biologics screen identifies materials for RNA delivery

    T. Chang, P. Shi, J. D. Steinmeyer, I. Chatnuntawech, P. Tillberg, K. T. Love, P. M. Eimon, D. G. Anderson and M. F. Yanik, Integr. Biol., 2014, 6, 926
    DOI: 10.1039/C4IB00150H

Search articles by author

Spotlight

Advertisements