Highly branched HK peptides are effective carriers of siRNA

Leng, Qixin; Scaria, Puthupparampil V.; Zhu, Jie; Ambulos, Nicholas P.; Campbell, Patricia; Mixson, A. James

doi:10.1002/jgm.748

Cited by 125 publications

(142 citation statements)

References 17 publications

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“…Rapid degradation of arginyl peptides by intracellular trypsin-like proteases could additionally account for the low cytotoxicity of the tested polypeptide (Futaki et al 2001b). Branched histidine and lysine polymers have been used in a similar manner for siRNA transfection approaches, demonstrating that the ability to successfully transfect DNA does not per se qualify for effective siRNA transfection (Leng et al 2005). Other approaches used siRNA chemically coupled to the membrane permeant peptides penetratin1 or transportan via a disulfide bond and have equally shown to mediate efficient transfection of primary neurons (Davidson et al 2004;Muratovska and Eccles 2004).…”

Section: Discussionmentioning

confidence: 99%

Stearylated octaarginine and artificial virus-like particles for transfection of siRNA into primary rat neurons

Tönges¹,

Lingor²,

Egle³

et al. 2006

RNA

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RNA interference (RNAi) provides a powerful experimental tool for sequence-specific gene silencing, allowing efficient analysis of gene function in a multitude of cell types. However, application of RNAi in primary mammalian neurons has been limited by low-transfection efficiency and considerable toxicity of conventional transfection methods. In this study, we evaluated a peptide-mediated and a polymer/lipid-based cellular delivery method for siRNA into rat primary neurons and compared the results with a commonly used liposomal transfection reagent. Stearylated octaarginine (Stearyl-R8) was used as polypeptide and artificial virus-like particles (AVPs) were used as a combined liposomal-polymeric vector, since both reagents have been previously shown to successfully transfect DNA into cell lines. Stearyl-R8 and AVPs both promoted siRNA transfection into primary hippocampal neurons via the endosomal pathway. SiRNA-mediated gene silencing could be effectively induced in primary neuron cultures. In comparison with the commonly used cationic liposome transfection agent, both novel reagents were less detrimental to cell metabolic activity. We conclude that these novel transfection methods yield performances comparable to cationic liposome-mediated transfection for siRNA, while being less cytotoxic in primary neurons. Stearyl-R8 and AVPs may therefore represent novel and more cost-efficient alternatives to conventional siRNA-transfection reagents.

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Section: Discussionmentioning

confidence: 99%

Stearylated octaarginine and artificial virus-like particles for transfection of siRNA into primary rat neurons

Tönges¹,

Lingor²,

Egle³

et al. 2006

RNA

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“…For instance, the modification of a polylysine dendritic scaffold with HIV tat protein sequences, which are described to be able to facilitate cellular and nuclear transport [148]; the modified polylysine dendrimers containing lipidated units developed by Bayele et al [149], which were able to efficiently deliver oligonucleotides into the nucleus; and the cell penetrating peptide bearing polylysine dendrimers developed by Toth and Minchin's group [150,151]. On the other hand, Mixson et al studied the effect of the histidine loading of different His/Lys-based dendrimers [152][153][154]. This was a development of his significantly enhanced DNA delivery in a variety of cell lines.…”

Section: Dendrimersmentioning

confidence: 99%

Peptide-Based Polymer Therapeutics

2014

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Abstract:Polypeptides are envisaged to achieve a major impact on a number of different relevant areas such as biomedicine and biotechnology. Acquired knowledge and the increasing interest on amino acids, peptides and proteins is establishing a large panel of these biopolymers whose physical, chemical and biological properties are ruled by their controlled sequences and composition. Polymer therapeutics has helped to establish these polypeptide-based constructs as polymeric nanomedicines for different applications, such as disease treatment and diagnostics. Herein, we provide an overview of the advantages of these systems and the main methodologies for their synthesis, highlighting the different polypeptide architectures and the current research towards clinical applications.

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“…Leng et al designed branched histidine-lysine (HK) peptides for the delivery of siRNAs and showed that H 3 K8b/siRNA polyplex inhibited beta-galactosidase expression by more than 80% in an endothelial cell line (SVR-bag4) (Leng et al, 2005). The work demonstrated that the histidine-rich domain and the terminal arms of H 3 K8 were crucial for siRNA delivery.…”

Section: Polypeptidesmentioning

confidence: 99%

Polymers in Small-Interfering RNA Delivery

Singha

Namgung

Kim

2011

Nucleic Acid Therapeutics

185

112

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This review will cover the current strategies that are being adopted to efficiently deliver small interfering RNA using nonviral vectors, including the use of polymers such as polyethylenimine, poly(lactic-co-glycolic acid), polypeptides, chitosan, cyclodextrin, dendrimers, and polymers-containing different nanoparticles. The article will provide a brief and concise account of underlying principle of these polymeric vectors and their structural and functional modifications which were intended to serve different purposes to affect efficient therapeutic outcome of small-interfering RNA delivery. The modifications of these polymeric vectors will be discussed with reference to stimuli-responsiveness, target specific delivery, and incorporation of nanoconstructs such as carbon nanotubes, gold nanoparticles, and silica nanoparticles. The emergence of small-interfering RNA as the potential therapeutic agent and its mode of action will also be mentioned in a nutshell.

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Highly branched HK peptides are effective carriers of siRNA

Cited by 125 publications

References 17 publications

Stearylated octaarginine and artificial virus-like particles for transfection of siRNA into primary rat neurons

Stearylated octaarginine and artificial virus-like particles for transfection of siRNA into primary rat neurons

Peptide-Based Polymer Therapeutics

Polymers in Small-Interfering RNA Delivery

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