Self-Assembled and Size-Controllable Oligonucleotide Nanospheres for Effective Antisense Gene Delivery through an Endocytosis-Independent Pathway

Angewandte Chemie
Jie ZhouHuanghao Yang

Abstract

The development of efficient gene delivery vectors has faced two major challenges, namely endo- and lysosomal escape and intracellular release. To address these problems, we developed an oligonucleotide (ON)-template-assisted polymerization approach to create ON nanospheres as gene vectors. Guanidinium-containing disulfide monomers were organized on the ON templates to increase their effective local concentrations. Consequently, ring-opening disulfide-exchange polymerization between monomers was accelerated, further facilitating the self-assembly of ON nanospheres. The size of these nanospheres was controlled by varying the length of the ON templates. Importantly, the nanospheres can be directly delivered into the cytosol through an endocytosis-independent pathway, which is followed by intracellular depolymerization in the reductive cytosolic environment to release the packaged ONs, resulting in efficient gene silencing. The ON nanospheres thus hold great promise as candidates for gene therapy.

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Citations

Jun 7, 2019·Angewandte Chemie·Yangyang ChengStefan Matile
Oct 12, 2019·Chembiochem : a European Journal of Chemical Biology·Quentin LaurentStefan Matile
Aug 29, 2020·Chemical Communications : Chem Comm·Si Si LiewShao Q Yao
Aug 31, 2020·Advanced Healthcare Materials·Xiaohui WuBaoquan Ding
Aug 25, 2020·Beilstein Journal of Organic Chemistry·Rémi MartinentStefan Matile
Sep 26, 2020·Chembiochem : a European Journal of Chemical Biology·Rémi MartinentStefan Matile
Apr 8, 2021·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Hongqian RenLiang Xu
Mar 30, 2021·Chemistry : a European Journal·Wei JiLi Li
Nov 21, 2020·Drug Discovery Today·Bo ChenGang Guo
Jun 5, 2021·Advanced Healthcare Materials·Luyao ShenYonggang Ke
Jun 25, 2021·Chemical Science·Yangyang ChengStefan Matile
Jul 2, 2021·Chemical Communications : Chem Comm·Fei LuBo Tang
Jun 27, 2021·Angewandte Chemie·Quentin LaurentStefan Matile
Aug 13, 2021·Advanced Healthcare Materials·Haihui WangHuanghao Yang
Aug 6, 2019·Journal of the American Chemical Society·Liping WangHuanghao Yang
Sep 2, 2021·JACS Au·Quentin LaurentStefan Matile

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