期刊
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
卷 58, 期 16, 页码 5236-5240出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.201813665
关键词
antisense agents; gene delivery; nanospheres oligonucleotides; self-assembly
资金
- National Natural Science Foundation of China [U1505221, 21622502, 21605023, 21635002]
- Natural Science Foundation of Fujian Province of China [2017J06004]
- Program for Changjiang Scholars and Innovative Research Team in University [IRT15R11]
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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