4.7 Article

A Multifunction Lipid-Based CRISPR-Cas13a Genetic Circuit Delivery System for Bladder Cancer Gene Therapy

期刊

ACS SYNTHETIC BIOLOGY
卷 9, 期 2, 页码 343-355

出版社

AMER CHEMICAL SOC
DOI: 10.1021/acssynbio.9b00349

关键词

genetic circuit delivery; CRISPR-Cas13a; liposome; gene therapy; bladder cancer

资金

  1. Postdoctoral Science Foundation of China [2018M643312]
  2. National Natural Science Foundation of China [81772737, 81773257]
  3. Natural Science Foundation of Guangdong Province [2018A030310644, 2017B030301015, 2018B030306023]
  4. Sanming Project of Shenzhen Health and Family Planning Commission [SZSM201412018, SZSM201512037]

向作者/读者索取更多资源

The treatment of bladder cancer has recently shown minimal progress. Gene therapy mediated by CRISPR provides a new option for bladder cancer treatment. In this study, we developed a versatile liposome system to deliver the CRISPR-Cas13a gene circuits into bladder cancer cells. After in vitro studies and intravesical perfusion studies in mice, this system showed five advantages: (1) CRISPR-Cas13a, a transcriptional targeting and cleavage tool for gene expression editing, did not affect the stability of the cell genome; (2) the prepared liposome systems were targeted to hVEGFR2, which is always highly expressed in bladder cancer cells; (3) the CRISPR-Cas13a sequence was driven by an artificial tumor specific promoter to achieve further targeting; (4) a near-infrared photosensitizer released using near-infrared light was introduced to control the delivery system; and (5) the plasmids were constructed with three crRNA tandem sequences to achieve multiple targeting and wider therapeutic results. This tumor cell targeting lipid delivery system with near-infrared laser-controlled ability provided a versatile strategy for CRISPR-Cas13a based gene therapy of bladder cancer.

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