Research Papers:

Targeted delivery of CRISPR/Cas9 to prostate cancer by modified gRNA using a flexible aptamer-cationic liposome

Shuai Zhen, Yoichiro Takahashi, Shunichi Narita, Yi-Chen Yang and Xu Li _

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Oncotarget. 2017; 8:9375-9387. https://doi.org/10.18632/oncotarget.14072

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Shuai Zhen1,2, Yoichiro Takahashi3, Shunichi Narita3, Yi-Chen Yang4, Xu Li1,2

1Center for Translational Medicine, The First Affiliated Hospital of Xi’an Jiaotong University, P.R. China

2Key Laboratory for Tumor Precision Medicine of Shaanxi Province, The First Affiliated Hospital of Xi’an Jiaotong University, P.R. China

3Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan

4Tsinghua University, School of Life Sciences, Beijing, China

Correspondence to:

Xu Li, email: [email protected]

Keywords: CRISPR/Cas9 delivery, aptamer-liposome chimera, prostate cancer, prostate-specific membrane antigen (PSMA), polo-like kinase 1 (PLK1)

Received: September 01, 2016     Accepted: December 06, 2016     Published: December 21, 2016


The potent ability of CRISPR/Cas9 system to inhibit the expression of targeted gene is being exploited as a new class of therapeutics for a variety of diseases. However, the efficient and safe delivery of CRISPR/Cas9 into specific cell populations is still the principal challenge in the clinical development of CRISPR/Cas9 therapeutics. In this study, a flexible aptamer-liposome-CRISPR/Cas9 chimera was designed to combine efficient delivery and increased flexibility. Our chimera incorporated an RNA aptamer that specifically binds prostate cancer cells expressing the prostate-specific membrane antigen as a ligand. Cationic liposomes were linked to aptamers by the post-insertion method and were used to deliver therapeutic CRISPR/Cas9 that target the survival gene, polo-like kinase 1, in tumor cells. We demonstrate that the aptamer-liposome-CRISPR/Cas9 chimeras had a significant cell-type binding specificity and a remarkable gene silencing effect in vitro. Furthermore, silencing promoted a conspicuous regression of prostate cancer in vivo. Importantly, the approach described here provides a universal means of cell type–specific CRISPR/Cas9 delivery, which is a critical goal for the widespread therapeutic applicability of CRISPR/Cas9 or other nucleic acid drugs.

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