Structure-function correlation of aminated poly(α)glutamate as siRNA nanocarriers.

Structure-function correlation of aminated poly(α)glutamate as siRNA nanocarriers. Biomacromolecules. 2016 Jul 5; Authors: Krivitsky A, Polyak D, Scomparin A, Eliyahu S, Ori A, Avkin Nachum S, Krivitsky V, Satchi-Fainaro R Abstract It has been two decades since cationic polymers were introduced to the world of oligonucleotides delivery. However, the optimal physico-chemical properties to make them a successful delivery vehicle are yet unknown. An ideal system became particularly interesting and necessary with the introduction of RNA interference as a promising therapeutic approach. Such nanocarrier should overcome challenges such as low plasma stability, poor cellular internalization and endosomal escape to induce gene silencing. To that end, we synthesized a library of biodegradable aminated poly(α)glutamate varied by amine moieties. In an attempt to elucidate the structure-function relationship, our polyplexes were physico-chemically characterized and their silencing activity and cytotoxicity were evaluated. We found several structures that demonstrated improved cellular internalization. These candidates silenced gene expression to less than 50% of their initial levels, while being safe to cells and mice. Based on our research, an improved and promising tailor-designed siRNA delivery platform can be developed. PMID: 27377188 [PubMed - as supplied by publisher]
Source: Biomacromolecules - Category: Biochemistry Authors: Tags: Biomacromolecules Source Type: research