Cellular siRNA delivery using cell-penetrating peptides modified for endosomal escape

Endoh, Tamaki; Ohtsuki, Takashi

doi:10.1016/j.addr.2009.04.005

Cited by 225 publications

(192 citation statements)

References 71 publications

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“…Last but not least, photochemical internalization (PCI) is a technique that aims to improve endosomal release. A photosensitizer is localized in the endosomal membrane and destabilizes the membrane upon illumination, triggering the release of endosomal content into cytosol (Berg, Kristian Selbo et al 1999;Endoh and Ohtsuki 2009).…”

Section: Endosomal Escapementioning

confidence: 99%

Endosomal Escape Pathways for Non-Viral Nucleic Acid Delivery Systems

Liang¹,

Lam²

2012

Molecular Regulation of Endocytosis

122

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Section: Endosomal Escapementioning

confidence: 99%

Endosomal Escape Pathways for Non-Viral Nucleic Acid Delivery Systems

Liang¹,

Lam²

2012

Molecular Regulation of Endocytosis

122

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“…Although viral vector delivery of oligonucleotides such as siRNA first appeared very promising in gene therapy of various diseases, its serious carcinogenic and immunogenic consequences casted doubt upon its therapeutic values. The positively charged or amphipathic CPPs are effective and less-toxic alternatives to the viral vectors for systemic and topical delivery of oligonucleotides such as siRNA (99)(100)(101). Recently, a Peptide Transduction Domain-ds (double-stranded) RNA Binding Domain (PTD-DRBD) fusion protein has been proposed for more efficient and non-cytotoxic siRNA delivery in variety of cellular models.…”

Section: Transdermal Drug Targetingmentioning

confidence: 99%

Cell‐penetrating Peptides as a Novel Transdermal Drug Delivery System

et al. 2012

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In the last decade, almost one-third of the newly discovered drugs approved by the US FDA were biomolecules and biologics. Effective delivery of therapeutic biomolecules to their target is a challenging issue. Innovations in drug delivery systems have improved the efficiency of many of new biopharmaceuticals. Designing of novel transdermal delivery systems has been one of the most important pharmaceutical innovations, which offers a number of advantages. The cell-penetrating peptides have been increasingly used to mediate delivery of bimolecular cargoes such as small molecules, small interfering RNA nucleotides, drug-loaded nanoparticles, proteins, and peptides, both in vitro and in vivo, without using any receptors and without causing any significant membrane damage. Among several different drug delivery routes, application of cell-penetrating peptides in the topical and transdermal delivery systems has recently garnered tremendous attention in both cosmeceutical and pharmaceutical research and industries. In this review, we discuss history of cell-penetrating peptides, cell-penetrating peptide ⁄ cargo complex formation, and their mechanisms of cell and skin transduction.

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“…Except less efficiency in vivo (Li & Huang, 2007), the nonviral vector (compared to the viral vector) is a convenient delivery strategy with low toxicity and ease of large-scale production. Cell penetrating peptide (CPP) can transfer various cargos including protein (Choi et al, 2006;ElAndaloussi et al, 2007;Nakase et al, 2008), nuclear acid (Eguchi et al, 2001;Endoh & Ohtsuki, 2009), and the other drug vector (Koppelhus et al, 2008) into a range of cell types as well as the blood-brain barrier (Lindgren et al, 2000). However, the negative charge of siRNA may neutralize the positive charges of CPPs either by covalent attachment (Meade & Dowdy, 2007) or noncovalent conjugated (Veldhoen et al, 2006;Meade & Dowdy, 2008), and result to reduce efficiency of CPP.…”

Section: Introductionmentioning

confidence: 99%

“…The dsRBD was also designed from different proteins, such as Protein kinase R (PKR), Dicer and Escherichia coli Ribonuclease III. The dsRBD was replaced with the two repeat segments of CPP-MPG: MPG-MPG (Endoh & Ohtsuki, 2009) to investigate if the magnitude of dsRBD parts combining with siRNA molecules in the complex would influence siRNA delivery. Six fusion proteins, as shown in Table 1, were designed as CPP-dsRBD-based siRNA vector.…”

Section: Introductionmentioning

confidence: 99%

Six-cell penetrating peptide-based fusion proteins for siRNA delivery

Tsui

2014

Drug Delivery

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The siRNA deliveries, for the siRNA's high negative charge, short serum half life, poor cellular internalization, etc, are still the key barriers for its application in clinic. In this study, several cell penetrating peptide (CPP) and dsRNA binding domain (dsRBD)-based fusion proteins have been developed and screened as the siRNA vector. The siRNA binding ability was measured by the agarose gel retardation, the cell uptaking was characterized under fluorescence microscopy, and further more RNAi effect was evaluated on the endogenous (GAPDH, western blot) and exogenous (GFP, flow cytometry analysis) genes in HeLa cell. Finally, the cytotoxicity was assessed on HeLa cells using cell counting kit-8. The efficiency of siRNA delivery by the CPP-dsRBD fusion protein was the CPP and the dsRBD dependent. Three fusion proteins showed similar efficiency of siRNA delivery when comparing to Lipofectamine RNAi Max as the siRNA carrier. These results indicated that these CPP-dsRBD-based fusion proteins were promising candidates as siRNA carriers.

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Cellular siRNA delivery using cell-penetrating peptides modified for endosomal escape

Cited by 225 publications

References 71 publications

Endosomal Escape Pathways for Non-Viral Nucleic Acid Delivery Systems

Endosomal Escape Pathways for Non-Viral Nucleic Acid Delivery Systems

Cell‐penetrating Peptides as a Novel Transdermal Drug Delivery System

Six-cell penetrating peptide-based fusion proteins for siRNA delivery

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