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...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Chen BL, Pan R, Askhatova D, Chen P
Formato: article
Lenguaje:EN
Publicado: Dove Medical Press 2015
Materias:
Acceso en línea:https://doaj.org/article/66224dd19e62424293bcca5f011d8305
Etiquetas: Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
id oai:doaj.org-article:66224dd19e62424293bcca5f011d8305
record_format dspace
spelling 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)
institution DOAJ
collection DOAJ
language EN
topic Medicine (General)
R5-920
spellingShingle 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
description 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 AT chenbl effectivesmallinterferingrnadeliveryinvitroviaanewstearylatedcationicpeptide
AT panr effectivesmallinterferingrnadeliveryinvitroviaanewstearylatedcationicpeptide
AT askhatovad effectivesmallinterferingrnadeliveryinvitroviaanewstearylatedcationicpeptide
AT chenp effectivesmallinterferingrnadeliveryinvitroviaanewstearylatedcationicpeptide
_version_ 1718402652452159488