Seraj, Sharmin Lee, Jinju Ahn, Hyung Jun 2024-01-19T19:31:59Z 2024-01-19T19:31:59Z 2022-01-10 2019-08 0006-2952 https://pubs.kist.re.kr/handle/201004/119703 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. English PERGAMON-ELSEVIER SCIENCE LTD GENE-EXPRESSION STABLE SUPPRESSION RNA INTERFERENCE IMMUNE-RESPONSES HAIRPIN RNAS SIRNA VECTORS NANOPARTICLES TRANSCRIPTION ACTIVATION Systemic delivery of Eg5 shRNA-expressing plasmids using PEGylated DC-Chol/DOPE cationic liposome: Long-term silencing and anticancer effects in vivo Article 10.1016/j.bcp.2019.05.021 1 BIOCHEMICAL PHARMACOLOGY, v.166, pp.192 - 202 BIOCHEMICAL PHARMACOLOGY 166 192 202 scie scopus 000474498800018 2-s2.0-85066399035 Pharmacology & Pharmacy Pharmacology & Pharmacy Article GENE-EXPRESSION STABLE SUPPRESSION RNA INTERFERENCE IMMUNE-RESPONSES HAIRPIN RNAS SIRNA VECTORS NANOPARTICLES TRANSCRIPTION ACTIVATION RNAi shRNA plasmid-based shRNA expression Long-term silencing PEGylated cationic liposome