HIV-1 Tat protein transduction domain peptide facilitates gene transfer in combination with cationic liposomes

Hyndman, Laura; Lemoine, Jérôme; Huang, Leaf; Porteous, David J.; Boyd, Alan; Nan, Xinsheng

doi:10.1016/j.jconrel.2004.07.023

Cited by 107 publications

(92 citation statements)

References 26 publications

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“…119 Using FACS analysis of live cells, Silhol et al 112 showed that the TAT basic domain entered proteoglycan-deficient CHO cells though the actual route of uptake was not identified. Transfection of A549 cells by lipoplexes (DOTAP or Lipofectin) decorated with TAT PTD, used here to presumably facilitate cytosolic entry, was inhibited by 41C but enhanced by chloroquine, 120 suggesting that an endocytic, possibly clathrin-mediated, pathway enabled uptake. While not indicated in this study, elsewhere clathrin-dependent uptake is implicated in transfection by lipoplexes alone, 121,122 although in each of these studies, a specific cell surface receptor is not identified as mediating cell entry.…”

Section: Intracellular Trafficking Of Nonviral Vectors Lk Medina-kauwmentioning

confidence: 85%

Intracellular trafficking of nonviral vectors

2005

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Section: Intracellular Trafficking Of Nonviral Vectors Lk Medina-kauwmentioning

confidence: 85%

Intracellular trafficking of nonviral vectors

2005

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“…The use of cell penetrating peptides, like the HIV peptide TAT, has the advantage of avoiding this pathway and taking the cargo directly into the cell. TAT-mediated cytoplasmic uptake of drug conjugated polymers [9,10], plasmid DNA [10], bacteriophages [11], magnetic nanoparticles of about 10-20 nm in diameter [12] and even liposomes having a diameter of 200 nm [13] has been documented in the literature [14][15][16][17]. Until now the mechanism of internalization of TAT peptide is unclear.…”

Section: Introductionmentioning

confidence: 99%

TAT peptide-based micelle system for potential active targeting of anti-cancer agents to acidic solid tumors

Sethuraman

Bae

2007

Journal of Controlled Release

318

205

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A novel drug targeting system for acidic solid tumors has been developed based on ultra pH sensitive polymer and cell penetrating TAT. The delivery system consisted of two components: 1) A polymeric micelle that has a hydrophobic core made of Poly(L-lactic acid) (PLLA) and a hydrophilic shell consisting of Polyethylene Glycol (PEG) conjugated to TAT (TATmicelle), 2) An ultra pH sensitive diblock copolymer of poly(methacryloyl sulfadimethoxine) (PSD) and PEG (PSD-b-PEG). The anionic PSD is complexed with cationic TAT of the micelles to achieve the final carrier, which could systemically shield the micelles and expose them at slightly acidic tumor pH. TATmicelles had particle sizes between 20 to 45 nm and their critical micelle concentrations were 3.5 mg/L to 5.5 mg/ L. The TATmicelles, upon mixing with pH sensitive PSD-b-PEG, showed slight increase in particle size between pH 8.0 and 6.8 (60-90 nm), indicating complexation. As the pH was decreased (pH 6.6 to 6.0) two populations were observed, one that of normal TAT micelles (45 nm) and the other of aggregated hydrophobic PSD-b-PEG. Zeta potential measurements showed similar trend substantiating the shielding/deshielding process. Flowcytometry and confocal microscopy showed significantly higher uptake of TAT micelles at pH 6.6 compared to pH 7.4 indicating shielding at normal pH and deshielding at tumor pH. The flowcytometry indicated that the TAT not only translocates into the cells but is also seen on the surface of the nucleus. These results strongly indicate that the above drug loaded micelles would be able to target any hydrophobic drug near the nucleus.

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“…The utilization of peptides has also recently been in the spotlight. Oligoarginine (R6, R8), 5 oligolysine and TAT (YGRKKRRQRRR), 6,7 for instance, have been grafted to DNA and delivered to various cell lines by taking advantage of the peptides' protein transduction abilities. 7 Other protein transduction domains (PTDs) such as antennapedia (Antp) of Drosophila or VP22 of herpes simplex virus seem to be less successful.…”

Section: Introductionmentioning

confidence: 99%

Nonviral Gene Delivery by a Novel Protein Transduction Domain

Park

2013

Bulletin of the Korean Chemical Society

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Gene therapy using nonviral gene delivery carriers has focused on the development and modification of synthetic carriers such as liposomes and polymers. Most polymers that are commercially used are taking advantage of their polycationic character which allows not only strong ligand-DNA affinity but also competent cell penetration. Despite the relatively high transfection efficiencies, high cytotoxicity is continuously pointed out as one of the major shortcomings of polycationic polymers such as PEI. Studies on the utilization of peptides have therefore been carried out recently to overcome these problems. For these reasons, the human transcription factor Hph-1, which is currently known as a protein transduction domain (PTD), was investigated in this study to evaluate its potential as a gene delivery carrier. Although its transfection efficiency was about 10-fold lower than PEI, it displayed almost no cytotoxicity even at concentrations as high as 100 µM. Hph-1 was oxidatively polymerized to yield poly-Hph-1. The cell viability of poly-Hph-1 transfected U87MG and NIH-3T3 cells was almost as high as the control (untreated) groups, and the transfection efficiency was about 10-fold higher than PEI. This study serves as a preliminary evaluation of Hph-1 and encourages further investigation.

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HIV-1 Tat protein transduction domain peptide facilitates gene transfer in combination with cationic liposomes

Cited by 107 publications

References 26 publications

Intracellular trafficking of nonviral vectors

Intracellular trafficking of nonviral vectors

TAT peptide-based micelle system for potential active targeting of anti-cancer agents to acidic solid tumors

Nonviral Gene Delivery by a Novel Protein Transduction Domain

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