Organ-targeted high-throughput in vivo biologics screen identifies materials for RNA delivery
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Anderson_Organ-targeted.pdf
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Author(s)
Chang, Tsung-Yao
Chatnuntawech, Itthi
Yanik, Mehmet Fatih
Tillberg, Paul W.
Eimon, Peter
Anderson, Daniel Griffith
Shi, Peng, Ph. D. Massachusetts Institute of Technology
Steinmeyer, Joseph Daly
Love, Kevin T
Date Issued
August 2014
Journal
Integrative Biology
Publisher
Royal Society of Chemistry
Citation
Chang, Tsung-Yao, Peng Shi, Joseph D. Steinmeyer, Itthi Chatnuntawech, Paul Tillberg, Kevin T. Love, Peter M. Eimon, Daniel G. Anderson, and Mehmet Fatih Yanik. “Organ-Targeted High-Throughput in Vivo Biologics Screen Identifies Materials for RNA Delivery.” Integr. Biol. 6, no. 10 (August 5, 2014): 926–934.
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Author's final manuscript
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.
MIT Department
Massachusetts Institute of Technology. Institute for Medical Engineering & Science
Harvard University--MIT Division of Health Sciences and Technology
Massachusetts Institute of Technology. Department of Chemical Engineering
Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science
Massachusetts Institute of Technology. Research Laboratory of Electronics
Koch Institute for Integrative Cancer Research at MIT
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DOI of Published Version
https://doi.org/10.1039/c4ib00150h
