Effective small interfering RNA delivery in vitro via a new stearylated cationic peptide
Baoling Chen,1,2 Ran Pan,1,2 Diana Askhatova,1 P Chen1,21Department of Chemical Engineering, 2Waterloo Institute for Nanotechnology, University of Waterloo, Waterloo, ON, CanadaAbstract: A crucial bottleneck in RNA interference-based gene therapy is the lack of safe and efficient delivery s...
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Dove Medical Press
2015
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oai:doaj.org-article:66224dd19e62424293bcca5f011d83052021-12-02T02:10:35ZEffective small interfering RNA delivery in vitro via a new stearylated cationic peptide1178-2013https://doaj.org/article/66224dd19e62424293bcca5f011d83052015-05-01T00:00:00Zhttp://www.dovepress.com/effective-small-interfering-rna-delivery-in-vitro-via-a-new-stearylate-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Baoling Chen,1,2 Ran Pan,1,2 Diana Askhatova,1 P Chen1,21Department of Chemical Engineering, 2Waterloo Institute for Nanotechnology, University of Waterloo, Waterloo, ON, CanadaAbstract: A crucial bottleneck in RNA interference-based gene therapy is the lack of safe and efficient delivery systems. Here, a novel small interfering RNA (siRNA) delivery peptide, STR-HK, was constructed by conjugating a stearyl end to the N-terminus of the peptide sequence HHHPKPKRKV, where PKPKRKV is an altered sequence of the nucleus localization signal (PKKKRKV) and contributes to the cytosol localization of STR-HK–siRNA complexes. Histidine is a linker and plays an important role in disrupting the endosomal membrane via the proton sponge effect. As expected, STR-HK formed complexes with siRNA with a particle size of 80–160 nm in diameter and efficiently delivered Cy3-labeled glyceraldehyde 3-phosphate dehydrogenase siRNA into PC-3 human prostate cancer cells. The transfection efficiency of STR-HK at molar ratio of 60/1 was comparable to that of Lipofectamine 2000, one of the most efficient commercially available transfection reagents. Furthermore, the STR-HK–siRNA complexes exhibited minimal cytotoxicity, which was significantly lower than that of Lipofectamine. Taken together, the strategy of conjugating the stearyl moiety with HHHPKPKRKV as a non-viral siRNA delivery system is advantageous.Keywords: RNA interference, cellular uptake, cytotoxicity, gene silencing, physicochemical characterizationChen BLPan RAskhatova DChen PDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2015, Iss default, Pp 3303-3314 (2015) |
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Medicine (General) R5-920 Chen BL Pan R Askhatova D Chen P Effective small interfering RNA delivery in vitro via a new stearylated cationic peptide |
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Baoling Chen,1,2 Ran Pan,1,2 Diana Askhatova,1 P Chen1,21Department of Chemical Engineering, 2Waterloo Institute for Nanotechnology, University of Waterloo, Waterloo, ON, CanadaAbstract: A crucial bottleneck in RNA interference-based gene therapy is the lack of safe and efficient delivery systems. Here, a novel small interfering RNA (siRNA) delivery peptide, STR-HK, was constructed by conjugating a stearyl end to the N-terminus of the peptide sequence HHHPKPKRKV, where PKPKRKV is an altered sequence of the nucleus localization signal (PKKKRKV) and contributes to the cytosol localization of STR-HK–siRNA complexes. Histidine is a linker and plays an important role in disrupting the endosomal membrane via the proton sponge effect. As expected, STR-HK formed complexes with siRNA with a particle size of 80–160 nm in diameter and efficiently delivered Cy3-labeled glyceraldehyde 3-phosphate dehydrogenase siRNA into PC-3 human prostate cancer cells. The transfection efficiency of STR-HK at molar ratio of 60/1 was comparable to that of Lipofectamine 2000, one of the most efficient commercially available transfection reagents. Furthermore, the STR-HK–siRNA complexes exhibited minimal cytotoxicity, which was significantly lower than that of Lipofectamine. Taken together, the strategy of conjugating the stearyl moiety with HHHPKPKRKV as a non-viral siRNA delivery system is advantageous.Keywords: RNA interference, cellular uptake, cytotoxicity, gene silencing, physicochemical characterization |
format |
article |
author |
Chen BL Pan R Askhatova D Chen P |
author_facet |
Chen BL Pan R Askhatova D Chen P |
author_sort |
Chen BL |
title |
Effective small interfering RNA delivery in vitro via a new stearylated cationic peptide |
title_short |
Effective small interfering RNA delivery in vitro via a new stearylated cationic peptide |
title_full |
Effective small interfering RNA delivery in vitro via a new stearylated cationic peptide |
title_fullStr |
Effective small interfering RNA delivery in vitro via a new stearylated cationic peptide |
title_full_unstemmed |
Effective small interfering RNA delivery in vitro via a new stearylated cationic peptide |
title_sort |
effective small interfering rna delivery in vitro via a new stearylated cationic peptide |
publisher |
Dove Medical Press |
publishDate |
2015 |
url |
https://doaj.org/article/66224dd19e62424293bcca5f011d8305 |
work_keys_str_mv |
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