Premium
Self‐Assembled and Size‐Controllable Oligonucleotide Nanospheres for Effective Antisense Gene Delivery through an Endocytosis‐Independent Pathway
Author(s) -
Zhou Jie,
Sun Liqin,
Wang Liping,
Liu Yichang,
Li Jinyu,
Li Jingying,
Li Juan,
Yang Huanghao
Publication year - 2019
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201813665
Subject(s) - endocytosis , oligonucleotide , gene delivery , monomer , intracellular , chemistry , cytosol , biophysics , template , polymerization , gene silencing , depolymerization , nanotechnology , microbiology and biotechnology , biochemistry , materials science , gene , polymer , transfection , biology , cell , polymer chemistry , enzyme , organic chemistry
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.