Abstract:
:Duration of gene silencing due to the short-term silencing effects induced by exogenous siRNA have limited the therapeutic applications of RNAi and the development of RNAi-based therapeutics. We here generated Eg5 shRNA-expressing plasmids using the inverted terminal repeats (ITRs) sequences to produce Eg5 hairpin RNA under the control of U6 promoter. Using PEGylated DC-Chol/DOPE cationic liposomes, we demonstrated that a single systemic administration of Eg5 shRNA-expressing plasmid/liposome lipoplexes induced the long-term Eg5 silencing in the tumor sites of tumor-bearing mice, and ultimately lead to more sustained anticancer effects than standard synthetic siEg5/liposome lipoplexes. This non-viral Eg5 shRNA expression system had no risk of immunogenicity anticipated in the use of viral vectors, and could reduce the potential of off-target effects by scaling down the administration dose of RNAi therapeutics in patient. Therefore, the sustainable shRNA expression properties in the tumor sites suggest an efficient strategy to overcome the limitations caused by chemically synthesized siRNA methods such as short-term silencing effects and off-target effects. Herein, this study provides a non-viral silencing strategy for inducing long-term Eg5 silencing in vivo and suggests the great potential of Eg5 shRNA-expressing lipoplexes as a DNA-based RNAi therapeutics for cancer treatment.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Seraj S,Lee J,Ahn HJdoi
10.1016/j.bcp.2019.05.021subject
Has Abstractpub_date
2019-08-01 00:00:00pages
192-202eissn
0006-2952issn
1873-2968pii
S0006-2952(19)30209-6journal_volume
166pub_type
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journal_title:Biochemical pharmacology
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journal_title:Biochemical pharmacology
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
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pub_type: 杂志文章
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更新日期:2017-11-15 00:00:00
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(90)90505-f
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pub_type: 杂志文章
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
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更新日期:1999-08-01 00:00:00
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(97)00196-2
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
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journal_title:Biochemical pharmacology
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
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pub_type: 杂志文章
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
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更新日期:2008-06-01 00:00:00
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(89)90625-4
更新日期:1989-10-01 00:00:00
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pub_type: 杂志文章
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更新日期:1993-06-22 00:00:00
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
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更新日期:1990-06-01 00:00:00
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2003.08.036
更新日期:2004-01-01 00:00:00