Exploration of peptide motifs for potent non‐viral gene delivery highly selective for dividing cells

Parker, Alan L.; Collins, Louise; Zhang, Xiaohong; Fabre, John W.

doi:10.1002/jgm.809

Cited by 19 publications

(20 citation statements)

References 34 publications

(90 reference statements)

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“…Synthetic peptides corresponding to these sequences have frequently been used as DNA vectors, with the idea of additionally assisting with translocation of the DNA plasmids into the nucleus, for review see [Cartier and Reszka 2002]. Interestingly, and somewhat surprisingly, simple (Lys) 16 [Colin et al 2001;Parker et al 2005;Shewring et al 1997] and possibly oligoarginine peptides [Tung et al 2002] also appear to have nuclear translocating ability. However, care is required, as substitution of these NLS peptides can sometimes abolish nuclear localising capacity (see later).…”

Section: (B) Cationic Peptidesmentioning

confidence: 97%

“…Small synthetic peptides rarely form secondary structure in aqueous solution, but these fusogenic peptides form stable alpha helices in solution [Haas and Murphy 2004;Li et al 2004;Parente et al 1988;Parker et al 2005]. Another key characteristic is the presence of a negatively charged amino acid every 3 or 4 amino acids in an otherwise hydrophobic sequence.…”

Section: I) Structure and Mechanism Of Actionmentioning

confidence: 97%

“…Although there are many complex factors to consider, these processes are easily demonstrated. Charge neutralisation can be shown by inhibition of the electrophoretic mobility of the DNA, when sufficient polycation is added [Parker et al 2005], Fig. (6).…”

Section: The Formation and Physical Properties Of Peptide/dna Particlesmentioning

confidence: 99%

“…for targeting [Hart et al 1995]. For example, we have extensively evaluated a 31 amino acid peptide consisting of (Lys) 16 for DNA binding, and the 15 amino acid, integrinbinding loop of molossin, a component of the venom of the American pit viper Crotalus molossus molossus for targeting [Shewring et al 1997], and a 39 amino acid peptide comprising an acid-dependent fusogenic peptide (for disruption of endocytic membranes) with (Lys) 16 at its carboxy terminus [Parker et al 2005 …”

Section: (E) Covalent Attachment Of Additional Functional Units To Thmentioning

confidence: 99%

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Synthetic Peptides As Non-Viral DNA Vectors

Fabre¹,

Collins²

2006

CGT

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The use of multiple peptide motifs to provide effective gene delivery holds great promise as an elegant, non-immunogenic approach to gene therapy. The molecular understanding of cell and viral biology provides a strong foundation on which to pursue this objective. Synthetic peptides containing multiple lysines and/or arginines (occasionally ornithines) provide natural polycations for multivalent electrostatic binding of DNA, and for DNA compaction into particles suitable for gene delivery. These cationic peptides can incorporate additional functional motifs (e.g. for translocating DNA into the nucleus) and they can be linked by disulphide bonds to produce high molecular reducible polycations with superior properties for gene therapy. Many factors influence the size, surface charge and stability of peptide/DNA particles. For in vivo use, uncharged particles resistant to disruption by salt and protein, and targeted to tissue-specific membrane molecules, will be required. Entry into the cell is via one of the endocytic pathways, depending on particle size and (in principle) the target cell surface molecule. Peptide motifs for endocytic escape are based mainly on the anionic fusogenic peptide of influenza virus haemagglutinin and on histidine-rich peptides (where the buffering properties of the imidazole group cause osmotic swelling and probably rupture of endocytic vesicles). Once in the cytosol, translocation of DNA plasmids across the nuclear pore complex into the nucleus is a crucial step, because most target cells for gene therapy are either non-dividing or slowly dividing. Nuclear translocation can be achieved by classical nuclear localising motifs, or more simply by (Lys)16 and other cationic peptides.

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Section: (B) Cationic Peptidesmentioning

confidence: 97%

Section: I) Structure and Mechanism Of Actionmentioning

confidence: 97%

Section: The Formation and Physical Properties Of Peptide/dna Particlesmentioning

confidence: 99%

Section: (E) Covalent Attachment Of Additional Functional Units To Thmentioning

confidence: 99%

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Synthetic Peptides As Non-Viral DNA Vectors

Fabre¹,

Collins²

2006

CGT

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“…90,91 A potential tumor-targeting peptide vector (cRGD-hK), which was intended to be systemically and repeatedly administered to patients with advanced solid tumors, was developed by Aoki et al 92 The peptide vector was composed of 36 amino-acid residues, CRGDCF(K[H-]KKK) 6 , incorporating a tumor-targeting RGD motif, a DNA-binding oligolysine and histidyl residues to facilitate the delivery into the cytosol (Figure 3c). In vitro (hepatoma and pancreatic cancer cells) transfection of the cRGD-hK/pDNA (luciferase expression plasmid) complexes was inhibited in the presence of either bafilomycin A1, which is an inhibitor of the vacuolar ATPase endosomal proton pump, or cycloRGDfV, which is an antagonist for integrin avb3.…”

Section: Rgd-functionalized Peptide-based Vectorsmentioning

confidence: 99%

A review of RGD-functionalized nonviral gene delivery vectors for cancer therapy

et al. 2012

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The development of effective treatments that enable many patients suffering from cancer to be successfully cured is highly demanded. Angiogenesis, which is a process for the formation of new capillary blood vessels, has a crucial role in solid tumor progression and the development of metastasis. Antiangiogenic therapy designed to prevent tumor angiogenesis, thereby arresting the growth or spread of tumors, has emerged as a non-invasive and safe option for cancer treatment. Due to the fact that integrin receptors are overexpressed on the surface of angiogenic endothelial cells, various strategies have been made to develop targeted delivery systems for cancer gene therapy utilizing integrin-targeting peptides with an exposed arginine-glycine-aspartate (RGD) sequence. The aim of this review is to summarize the progress and prospect of RGD-functionalized nonviral vectors toward targeted delivery of genetic materials in order to achieve an efficient therapeutic outcome for cancer gene therapy, including antiangiogenic therapy.

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A fusogenic segment of glycoprotein H from herpes simplex virus enhances transfection efficiency of cationic liposomes

Kim

2008

The Journal of Gene Medicine

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Exploration of peptide motifs for potent non‐viral gene delivery highly selective for dividing cells

Cited by 19 publications

References 34 publications

Synthetic Peptides As Non-Viral DNA Vectors

Synthetic Peptides As Non-Viral DNA Vectors

A review of RGD-functionalized nonviral gene delivery vectors for cancer therapy

A fusogenic segment of glycoprotein H from herpes simplex virus enhances transfection efficiency of cationic liposomes

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