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Melamine Functionalized Copolymer for Sequence Specific siRNA Loading and Ligand-Driven Delivery

Xia, Xin X. and Zhou, Zhun and DeSantis, Christopher and Rossi, John and Bong, Dennis (2018) Melamine Functionalized Copolymer for Sequence Specific siRNA Loading and Ligand-Driven Delivery. Molecular Therapy, 26 (5). p. 285. ISSN 1525-0016. https://resolver.caltech.edu/CaltechAUTHORS:20180706-153010023

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Abstract

Triamino triazine, also termed melamine, presents three identical interfaces that are capable of recognizing U/T with three hydrogen bonds. When displayed on a polymeric chain, melamine displaying polymers are capable of condensing structureless U/T tracts into triple-stranded structures, which have been conferred with enhanced tolerance towards nuclease degradation and preserved biological function. In this study, a mixed-block copolymer with alternating display of N-Acetylgalactosamine (GalNAc) and melamine p(GM)_(10) is synthesized via reversible addition-fragmentation chain transfer (RAFT). The polymer has been demonstrated to sequence specifically load the 27-mer dicer substrate siRNA targeting ApoB-100 precursor mRNA that is appended with U stretches. The loaded siRNA can be efficiently processed by recombinant dicer, and readily uptaken by HepG2 cells via receptor mediated endocytosis, eliciting an IC 50 of 5 nM. Further, the copolymer is immunologically tolerant as the result of carbohydrate decoration, and induces minimum cytokine release syndrome. Hence, melamine displaying polymer offers a novel siRNA delivery strategy with enhanced RNAi potency; further, RAFT polymerization has been demonstrated to be a versatile platform for synthesizing tailored delivery system with tissue/disease-specific ligand conjugations.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1016/j.ymthe.2018.05.001DOIAbstracts
Additional Information:© 2018 American Society of Gene & Cell Therapy. Available online 9 May 2018.
Issue or Number:5
Record Number:CaltechAUTHORS:20180706-153010023
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20180706-153010023
Official Citation:ASGCT 21st Annual Meeting Abstracts, Molecular Therapy, Volume 26, Issue 5, Supplement 1, 2018, Pages 1-459, ISSN 1525-0016, https://doi.org/10.1016/j.ymthe.2018.05.001. (http://www.sciencedirect.com/science/article/pii/S1525001618302041)
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:87620
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:06 Jul 2018 22:41
Last Modified:03 Oct 2019 19:57

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