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Targeted Delivery of CRISPR/Cas9‐Mediated Cancer Gene Therapy via Liposome‐Templated Hydrogel Nanoparticles
Author(s) -
Chen Zeming,
Liu Fuyao,
Chen Yanke,
Liu Jun,
Wang Xiaoying,
Chen Ann T.,
Deng Gang,
Zhang Hongyi,
Liu Jie,
Hong Zhangyong,
Zhou Jiangbing
Publication year - 2017
Publication title -
advanced functional materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.069
H-Index - 322
eISSN - 1616-3028
pISSN - 1616-301X
DOI - 10.1002/adfm.201703036
Subject(s) - crispr , cas9 , genome editing , genetic enhancement , computational biology , biology , cancer research , materials science , gene , nanotechnology , genetics
Due to its simplicity, versatility, and high efficiency, the clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 technology has emerged as one of the most promising approaches for treatment of a variety of genetic diseases, including human cancers. However, further translation of CRISPR/Cas9 for cancer gene therapy requires development of safe approaches for efficient, highly specific delivery of both Cas9 and single guide RNA to tumors. Here, novel core–shell nanostructure, liposome‐templated hydrogel nanoparticles (LHNPs) that are optimized for efficient codelivery of Cas9 protein and nucleic acids is reported. It is demonstrated that, when coupled with the minicircle DNA technology, LHNPs deliver CRISPR/Cas9 with efficiency greater than commercial agent Lipofectamine 2000 in cell culture and can be engineered for targeted inhibition of genes in tumors, including tumors the brain. When CRISPR/Cas9 targeting a model therapeutic gene, polo‐like kinase 1 (PLK1), is delivered, LHNPs effectively inhibit tumor growth and improve tumor‐bearing mouse survival. The results suggest LHNPs as versatile CRISPR/Cas9‐delivery tool that can be adapted for experimentally studying the biology of cancer as well as for clinically translating cancer gene therapy.