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Highly efficient delivery of siRNA to a heart transplant model by a novel cell penetrating peptide-dsRNA binding domain

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Highly efficient delivery of siRNA to a heart transplant model by a novel cell penetrating peptide-dsRNA binding domain. / Li, Hua; Zheng, Xiangtao; Koren, Viktoria; Vashist, Yogesh Kumar; Tsui, Tung Yu.

in: INT J PHARMACEUT, Jahrgang 469, Nr. 1, 20.07.2014, S. 206-13.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Li, H, Zheng, X, Koren, V, Vashist, YK & Tsui, TY 2014, 'Highly efficient delivery of siRNA to a heart transplant model by a novel cell penetrating peptide-dsRNA binding domain', INT J PHARMACEUT, Jg. 469, Nr. 1, S. 206-13. https://doi.org/10.1016/j.ijpharm.2014.04.050

APA

Li, H., Zheng, X., Koren, V., Vashist, Y. K., & Tsui, T. Y. (2014). Highly efficient delivery of siRNA to a heart transplant model by a novel cell penetrating peptide-dsRNA binding domain. INT J PHARMACEUT, 469(1), 206-13. https://doi.org/10.1016/j.ijpharm.2014.04.050

Vancouver

Li H, Zheng X, Koren V, Vashist YK, Tsui TY. Highly efficient delivery of siRNA to a heart transplant model by a novel cell penetrating peptide-dsRNA binding domain. INT J PHARMACEUT. 2014 Jul 20;469(1):206-13. https://doi.org/10.1016/j.ijpharm.2014.04.050

Bibtex

@article{b15cf412010440f3931ba80d8a5f7c8f,
title = "Highly efficient delivery of siRNA to a heart transplant model by a novel cell penetrating peptide-dsRNA binding domain",
abstract = "Small interfering RNAs (siRNAs) delivery remains a bottleneck for RNA interference (RNAi) - based therapies in the clinic. In the present study, a fusion protein with two cell-penetrating peptides (CPP), Hph1-Hph1, and a double-stranded RNA binding domain (dsRBD), was constructed for the siRNA delivery: dsRBD was designed to bind siRNA, and CPP would subsequently transport the dsRBD/siRNA complex into cells. We assessed the efficiency of the fusion protein, Hph1-Hph1-dsRBD, as a siRNA carrier. Calcium-condensed effects were assessed on GAPDH and green fluorescent protein (GFP) genes by western blot, real time polymerase chain reaction (RT-PCR), and flow cytometry analysis in vitro. Evaluations were also made in an in vivo heart transplantation model. The results demonstrated that the fusion protein, Hph1-Hph1-dsRBD, is highly efficient at delivering siRNA in vitro, and exhibits efficiency on GAPDH and GFP genes similar to or greater than lipofectamine. Interestingly, the calcium-condensed effects dramatically enhanced cellular uptake of the protein-siRNA complex. In vivo, Hph1-Hph1-dsRBD transferred and distributed ^ targeted siRNA throughout the whole mouse heart graft. Together, these results indicate that Hph1-Hph1-dsRBD has potential as an siRNA carrier for applications in the clinic or in biomedical research.",
keywords = "Animals, Biological Transport, Calcium, Cell-Penetrating Peptides, Gene Expression Regulation, Gene Transfer Techniques, Genes, Reporter, Genetic Therapy, Glyceraldehyde-3-Phosphate Dehydrogenases, Green Fluorescent Proteins, HeLa Cells, Heart Transplantation, Humans, Male, Mice, Inbred C57BL, Peptide Fragments, Protein Interaction Domains and Motifs, RNA Interference, RNA, Small Interfering, RNA-Binding Proteins, Recombinant Fusion Proteins",
author = "Hua Li and Xiangtao Zheng and Viktoria Koren and Vashist, {Yogesh Kumar} and Tsui, {Tung Yu}",
note = "Copyright {\textcopyright} 2014 Elsevier B.V. All rights reserved.",
year = "2014",
month = jul,
day = "20",
doi = "10.1016/j.ijpharm.2014.04.050",
language = "English",
volume = "469",
pages = "206--13",
journal = "INT J PHARMACEUT",
issn = "0378-5173",
publisher = "Elsevier",
number = "1",

}

RIS

TY - JOUR

T1 - Highly efficient delivery of siRNA to a heart transplant model by a novel cell penetrating peptide-dsRNA binding domain

AU - Li, Hua

AU - Zheng, Xiangtao

AU - Koren, Viktoria

AU - Vashist, Yogesh Kumar

AU - Tsui, Tung Yu

N1 - Copyright © 2014 Elsevier B.V. All rights reserved.

PY - 2014/7/20

Y1 - 2014/7/20

N2 - Small interfering RNAs (siRNAs) delivery remains a bottleneck for RNA interference (RNAi) - based therapies in the clinic. In the present study, a fusion protein with two cell-penetrating peptides (CPP), Hph1-Hph1, and a double-stranded RNA binding domain (dsRBD), was constructed for the siRNA delivery: dsRBD was designed to bind siRNA, and CPP would subsequently transport the dsRBD/siRNA complex into cells. We assessed the efficiency of the fusion protein, Hph1-Hph1-dsRBD, as a siRNA carrier. Calcium-condensed effects were assessed on GAPDH and green fluorescent protein (GFP) genes by western blot, real time polymerase chain reaction (RT-PCR), and flow cytometry analysis in vitro. Evaluations were also made in an in vivo heart transplantation model. The results demonstrated that the fusion protein, Hph1-Hph1-dsRBD, is highly efficient at delivering siRNA in vitro, and exhibits efficiency on GAPDH and GFP genes similar to or greater than lipofectamine. Interestingly, the calcium-condensed effects dramatically enhanced cellular uptake of the protein-siRNA complex. In vivo, Hph1-Hph1-dsRBD transferred and distributed ^ targeted siRNA throughout the whole mouse heart graft. Together, these results indicate that Hph1-Hph1-dsRBD has potential as an siRNA carrier for applications in the clinic or in biomedical research.

AB - Small interfering RNAs (siRNAs) delivery remains a bottleneck for RNA interference (RNAi) - based therapies in the clinic. In the present study, a fusion protein with two cell-penetrating peptides (CPP), Hph1-Hph1, and a double-stranded RNA binding domain (dsRBD), was constructed for the siRNA delivery: dsRBD was designed to bind siRNA, and CPP would subsequently transport the dsRBD/siRNA complex into cells. We assessed the efficiency of the fusion protein, Hph1-Hph1-dsRBD, as a siRNA carrier. Calcium-condensed effects were assessed on GAPDH and green fluorescent protein (GFP) genes by western blot, real time polymerase chain reaction (RT-PCR), and flow cytometry analysis in vitro. Evaluations were also made in an in vivo heart transplantation model. The results demonstrated that the fusion protein, Hph1-Hph1-dsRBD, is highly efficient at delivering siRNA in vitro, and exhibits efficiency on GAPDH and GFP genes similar to or greater than lipofectamine. Interestingly, the calcium-condensed effects dramatically enhanced cellular uptake of the protein-siRNA complex. In vivo, Hph1-Hph1-dsRBD transferred and distributed ^ targeted siRNA throughout the whole mouse heart graft. Together, these results indicate that Hph1-Hph1-dsRBD has potential as an siRNA carrier for applications in the clinic or in biomedical research.

KW - Animals

KW - Biological Transport

KW - Calcium

KW - Cell-Penetrating Peptides

KW - Gene Expression Regulation

KW - Gene Transfer Techniques

KW - Genes, Reporter

KW - Genetic Therapy

KW - Glyceraldehyde-3-Phosphate Dehydrogenases

KW - Green Fluorescent Proteins

KW - HeLa Cells

KW - Heart Transplantation

KW - Humans

KW - Male

KW - Mice, Inbred C57BL

KW - Peptide Fragments

KW - Protein Interaction Domains and Motifs

KW - RNA Interference

KW - RNA, Small Interfering

KW - RNA-Binding Proteins

KW - Recombinant Fusion Proteins

U2 - 10.1016/j.ijpharm.2014.04.050

DO - 10.1016/j.ijpharm.2014.04.050

M3 - SCORING: Journal article

C2 - 24768403

VL - 469

SP - 206

EP - 213

JO - INT J PHARMACEUT

JF - INT J PHARMACEUT

SN - 0378-5173

IS - 1

ER -