Peptides in DNA delivery: current insights and future directions

Mann, Anita; Thakur, Garima; Shukla, Vivek Kumar; Ganguli, Munia

doi:10.1016/j.drudis.2007.11.008

Cited by 62 publications

(62 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…For this purpose, DNA condensation is a recurrent requisite for this type of nonviral therapeutic approach. 5,[8][9][10][11][12] Bloomfield 13 has defined DNA condensation as the collapse of extended DNA chains into compact, orderly particles containing only one or a few molecules. Typically, this process results from a neutralization of the negative charges of the DNA phosphate groups with transition into the ordered phase that occurs when 90% of charges are neutralized.…”

Section: Introductionmentioning

confidence: 99%

“…13 Different systems have been proposed and tested for nonviral gene delivery based on DNA condensation and protection. 12,14,15 However, the drawback of this therapeutic approach is often the lack of a successful in vivo application. There is clearly a need to develop highly efficient, chemical, nonviral gene carriers that can protect DNA and persist under physiological in vivo conditions.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Fatty acid–spermine conjugates as DNA carriers for nonviral in vivo gene delivery

et al. 2009

View full text Add to dashboard Cite

The lack of efficient in vivo gene delivery is a well-known shortcoming of nonviral delivery vectors, in particular of chemical vectors. We developed a series of novel nonviral carriers for plasmid-based in vivo gene delivery. This new transport device is based on the assembly of DNA plasmids with synthetic derivatives of naturally occurring moleculesfatty acid-spermine conjugates (or lipospermines). We tested the ability of these fatty acid conjugates to interact with plasmid DNA (pDNA) and found that they formed DNA nanocomplexes, which are protected from DNase I degradation. This protection was shown to directly correlate with the length of the aliphatic component. However, this increase in the length of the hydrocarbon chain resulted in increased toxicity. The cationic lipids used for transfection typically have a C 16 and C 18 hydrocarbon chain. Interestingly, toxicity studies, together with further characterization studies, suggested that the two most suitable candidates for in vivo delivery are those with the shortest hydrocarbon chain, butanoyl-and decanoylspermine. Morphological characterization of DNA nanocomplexes resulting from these lipospermines showed the formation of a homogenous population, with the diameter ranging approximately from 40 to 200 nm. Butanoylspermine was found to be the most promising carrier from this series, resulting in a significantly increased gene expression, in relation to naked plasmid, in both tissues herein targeted (dermis and M. tibialis anterior). Thus, we established a correlation between the in vitro properties of the ensuing DNA nanocarriers and their efficient in vivo gene expression.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Fatty acid–spermine conjugates as DNA carriers for nonviral in vivo gene delivery

et al. 2009

View full text Add to dashboard Cite

show abstract

“…TAT peptide) and often with simple chemical modifications like attachment of other additional amino-acids, polyethylene glycol, functional moieties like targeting ligands, and fusogenic peptides, etc. are the most commonly studied peptide based gene delivery agents (22,23). We show that the 16-mer arginine and lysine homopeptides differ in their requirement of cell surface GAGs as well as in their interaction with soluble GAGs during gene delivery.…”

mentioning

confidence: 99%

Exogenous and Cell Surface Glycosaminoglycans Alter DNA Delivery Efficiency of Arginine and Lysine Homopeptides in Distinctly Different Ways

Naik¹,

Chandra

Mann³

et al. 2011

Journal of Biological Chemistry

View full text Add to dashboard Cite

Glycosaminoglycans (GAGs) expressed ubiquitously on the cell surface are known to interact with a variety of ligands to mediate different cellular processes. However, their role in the internalization of cationic gene delivery vectors such as liposomes, polymers, and peptides is still ambiguous and seems to be controlled by multiple factors. In this report, taking peptides as model systems, we show that peptide chemistry is one of the key factors that determine the dependence on cell surface glycosaminoglycans for cellular internalization and gene delivery. Arginine peptides and their complexes with plasmid DNA show efficient uptake and functional gene transfer independent of the cell surface GAGs. On the other hand, lysine peptides and complexes primarily enter through a GAG-dependent pathway. The peptide-DNA complexes also show differential interaction with soluble GAGs. In the presence of exogenous GAGs under certain conditions, arginine peptide-DNA complexes show increased transfection efficiency that is not observed with lysine. This is attributed to a change in the complex nature that ensures better protection of the compacted DNA in the case of arginine complexes, whereas the lysine complexes get destabilized under these conditions. The presence of a GAG coating also ensures better cell association of arginine complexes, resulting in increased uptake. Our results indicate that the role of both the cell surface and exogenous glycosaminoglycans in gene delivery is controlled by the nature of the peptide and its complex with DNA.

show abstract

“…However, a major limitation in DNA vaccination is the safe delivery of genetic material into target cells through the plasma and nuclear membranes [53,54]. Several CPPs, including the herpes simplex virus (HSV-1) protein VP22 and TAT, have been exploited for the delivery of genetic materials into cells [1,55]. To evaluate the potential of GV1001 for DNA delivery, we added polylysine (15-mer) to the carboxyl-terminus of GV1001 (GV1001-pK) and investigated whether non-covalently linked DNA was transferred into the cell.…”

Section: Delivery Of Macromolecules By Gv1001mentioning

confidence: 99%

The Telomerase-Derived Anticancer Peptide Vaccine GV1001 as an Extracellular Heat Shock Protein-Mediated Cell-Penetrating Peptide

Kim

Seo

Lee

et al. 2016

Preprint

View full text Add to dashboard Cite

Cell-penetrating peptides (CPPs), which can facilitate the transport of molecular cargo across the plasma membrane, have become important tools in promoting the cellular delivery of macromolecules. GV1001, a peptide derived from a reverse-transcriptase subunit of telomerase (hTERT) and developed as a vaccine against various cancers, reportedly has unexpected CPP properties. Unlike typical CPPs, such as the HIV-1 TAT peptide, GV1001 enabled the cytosolic delivery of macromolecules such as proteins, DNA and siRNA via extracellular heat shock protein 90 (eHSP90) and 70 (eHSP70) complexes. The eHSP-GV1001 interaction may have biological effects in addition to its cytosolic delivery function. GV1001 was originally designed as a major histocompatibility complex (MHC) class II-binding cancer epitope, but its CPP properties may contribute to its strong anti-cancer immune response relative to other telomerase peptide-based vaccines. Cell signaling via eHSP-GV1001 binding may lead to unexpected biological effects, such as direct anticancer or antiviral effects. In this review, we focus on the CPP effects of GV1001 bound to eHSP90 and eHSP70.

show abstract

Peptides in DNA delivery: current insights and future directions

Cited by 62 publications

References 59 publications

Fatty acid–spermine conjugates as DNA carriers for nonviral in vivo gene delivery

Fatty acid–spermine conjugates as DNA carriers for nonviral in vivo gene delivery

Exogenous and Cell Surface Glycosaminoglycans Alter DNA Delivery Efficiency of Arginine and Lysine Homopeptides in Distinctly Different Ways

The Telomerase-Derived Anticancer Peptide Vaccine GV1001 as an Extracellular Heat Shock Protein-Mediated Cell-Penetrating Peptide

Contact Info

Product

Resources

About