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Highly efficient delivery of siRNA to a heart transplant model by a novel cell penetrating peptide-dsRNA binding domain.
- Source :
-
International Journal of Pharmaceutics . Jul2014, Vol. 469 Issue 1, p206-213. 8p. - Publication Year :
- 2014
-
Abstract
- 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. [Copyright &y& Elsevier]
Details
- Language :
- English
- ISSN :
- 03785173
- Volume :
- 469
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- International Journal of Pharmaceutics
- Publication Type :
- Academic Journal
- Accession number :
- 96239907
- Full Text :
- https://doi.org/10.1016/j.ijpharm.2014.04.050