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タイトル: | Targeted delivery of CRISPR/Cas9 to prostate cancer by modified gRNA using a flexible aptamer-cationic liposome |
著者: | Zhen, Shuai Takahashi, Y. Narita, S. Yang, Yi-Chen Li, Xu |
キーワード: | CRISPR/Cas9 delivery aptamer-liposome chimera prostate cancer prostate-specific membrane antigen (PSMA) polo-like kinase 1 (PLK1) |
発行日: | 21-Dec-2016 |
出版者: | Impact Journals, LLC |
誌名: | Oncotarget |
抄録: | 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. |
著作権等: | All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License. |
URI: | http://hdl.handle.net/2433/218755 |
DOI(出版社版): | 10.18632/oncotarget.14072 |
PubMed ID: | 28030843 |
出現コレクション: | 学術雑誌掲載論文等 |
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