Cell-Based GATA4 Cardiac Gene Transfer Using Cell-Penetrating Peptide

Tang, Tong; Hammond, H. Kirk

doi:10.1161/circresaha.107.101102

Cited by 3 publications

(2 citation statements)

References 36 publications

(36 reference statements)

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“…Current gene research focuses on two CPPs: Tat, originating from HIV type 1, and pAntp, isolated from the transcription factor Antennapedia. They can transport plasmid DNA, siR-NA, liposomes, etc., across plasma membranes (Tang and Hammond, 2007;Koren and Torchilin, 2012). Bian at al.…”

Section: Cell-penetrating Peptidesmentioning

confidence: 99%

Myocardial Gene Transfer: Routes and Devices for Regulation of Transgene Expression by Modulation of Cellular Permeability

Katz

Fargnoli²,

Bridges³

2013

Human Gene Therapy

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Heart diseases are major causes of morbidity and mortality in Western society. Gene therapy approaches are becoming promising therapeutic modalities to improve underlying molecular processes affecting failing cardiomyocytes. Numerous cardiac clinical gene therapy trials have yet to demonstrate strong positive results and advantages over current pharmacotherapy. The success of gene therapy depends largely on the creation of a reliable and efficient delivery method. The establishment of such a system is determined by its ability to overcome the existing biological barriers, including cellular uptake and intracellular trafficking as well as modulation of cellular permeability. In this article, we describe a variety of physical and mechanical methods, based on the transient disruption of the cell membrane, which are applied in nonviral gene transfer. In addition, we focus on the use of different physiological techniques and devices and pharmacological agents to enhance endothelial permeability. Development of these methods will undoubtedly help solve major problems facing gene therapy.

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Section: Cell-penetrating Peptidesmentioning

confidence: 99%

Myocardial Gene Transfer: Routes and Devices for Regulation of Transgene Expression by Modulation of Cellular Permeability

Katz

Fargnoli²,

Bridges³

2013

Human Gene Therapy

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“…This significant discovery has inspired a series of efforts to apply VP22 as a therapeutic intercellular delivery vehicle by fusing different exogenous genes to it. So far, VP22 has been successfully expressed and trafficked in more than 10 cell lines and several VP22 fusion proteins have been successfully delivered between cells without disturbing the functions of the fused genes [39][40][41][42][43]. The VP22 mediated gene delivery precludes the need of using viral vectors for a high modification efficacy.…”

Section: Introductionmentioning

confidence: 99%

The Study of the Intercellular Trafficking of the Fusion Proteins of Herpes Simplex Virus Protein VP22

2014

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BackgroundGenetic modifications can improve the therapeutic efficacy of mesenchymal stem cell (MSC) transplantation in myocardial infarction. However, so far, the efficiency of MSC modification is very low. Seeking for a more efficient way of MSC modification, we investigated the possibility of employing the intercellular trafficking capacity of the herpes simplex virus type-1 tegument protein VP22 on the enhancement of MSC modification.MethodsPlasmids pVP22-myc, pVP22-EGFP, pEGFP-VP22, pVP22-hBcl-xL and phBcl-xL-VP22 were constructed for the expressions of the myc-tagged VP22 and the fusion proteins VP22-EGFP, EGFP-VP22, VP22-hBcl-xL and hBcl-xL-VP22. MSCs were isolated from rat bone marrow and the surface markers were identified by Flowcytometry. COS-1 cells were transfected with the above plasmids and co-cultured with untransfected MSCs, the intercellular transportations of the constructed proteins were studied by immunofluorescence. The solubility of VP22-hBcl-xL and hBcl-xL-VP22 was analyzed by Western blot.ResultsVP22-myc could be expressed in and spread between COS-1 cells, which indicates the validity of our VP22 expression construct. Flowcytometry analysis revealed that the isolated MSCs were CD29, CD44, and CD90 positive and were negative for the hematopoietic markers, CD34 and CD45. The co-culturing and immunofluorescence assay showed that VP22-myc, VP22-EGFP and EGFP-VP22 could traffic between COS-1 cells and MSCs, while the evidence of intercellular transportation of VP22-hBcl-xL and hBcl-xL-VP22 was not detected. Western blot analysis showed that VP22-hBcl-xL and hBcl-xL-VP22 were both insoluble in the cell lysate suggesting interactions of the fusion proteins with other cellular components.ConclusionsThe intercellular trafficking of VP22-myc, VP22-EGFP and EGFP-VP22 between COS-1 cells and MSCs presents an intriguing prospect in the therapeutic application of VP22 as a delivery vehicle which enhances genetic modifications of MSCs. However, VP22-hBcl-xL and hBcl-xL-VP22 failed to spread between cells, which are due to the insolubility of the fusion protein incurred by interactions with other cellular components.

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Antiapoptotic fusion protein delivery systems

Tan

Kim

2008

Macromol. Res.

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Apoptosis is a natural cell suicide mechanism to maintain homeostasis. However, many of the diseases encountered today are caused by aberrant apoptosis where excessive apoptosis leads to neurodegenerative disorders, ischemic heart disease, autoimmune disorders, infectious diseases, etc. A variety of antiapoptotic agents have been reported to interfere with the apoptosis pathway. These agents can be potential drug candidates for the treatment or prevention of diseases caused by dysregulated apoptosis. Obviously, world-wide pharmaceutical and biotechnology companies are gearing up to develop antiapoptotic drugs with some products being commercially available. Polymeric drug delivery systems are essential to their success. Recent R&D efforts have focused on the chemical or bioconjugation of antiapoptotic proteins with the protein transduction domain (PTD) for higher cellular uptake with antibodies for specific targeting as well as with polymers to enhance the protein stability and prolonged effect with success observed both in vivo and in vitro. All these different fusion antiapoptotic proteins provide promising results for the treatment of dysregulated apoptosis diseases.

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Cell-Based GATA4 Cardiac Gene Transfer Using Cell-Penetrating Peptide

Cited by 3 publications

References 36 publications

Myocardial Gene Transfer: Routes and Devices for Regulation of Transgene Expression by Modulation of Cellular Permeability

Myocardial Gene Transfer: Routes and Devices for Regulation of Transgene Expression by Modulation of Cellular Permeability

The Study of the Intercellular Trafficking of the Fusion Proteins of Herpes Simplex Virus Protein VP22

Antiapoptotic fusion protein delivery systems

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