Current Issue : July - September Volume : 2015 Issue Number : 3 Articles : 5 Articles
A biomimic reconstituted high density lipoprotein (rHDL) based system, rHDL/Stearic-PEI/VEGF complexes, was fabricated\nas an advanced nanovector for delivering VEGF plasmid. Here, Stearic-PEI was utilized to effectively condense VEGF plasmid\nand to incorporate the plasmid into rHDL. The rHDL/Stearic-PEI/VEGF complexes with diameter under 100 nm and neutral\nsurface charge demonstrated enhanced stability under the presence of bovine serum albumin. Moreover, in vitro cytotoxicity\nand transfection assays on H9C2 cells further revealed their superiority, as they displayed lower cytotoxicity with much higher\ntransfection efficiencywhen compared to PEI 10K/VEGF and Lipos/Stearic-PEI/VEGF complexes. In addition, in vivo investigation\non ischemia/reperfusion rat model implied that rHDL/Stearic-PEI/VEGF complexes possessed high transgene capacity and strong\ntherapeutic activity. These findings indicated that rHDL/Stearic-PEI/VEGF complexes could be an ideal gene delivery system for\nenhanced VEGF gene therapy of myocardial ischemia, which might be a new promising strategy for effective myocardial ischemia\ntreatment....
Recent progress in neural stem cell- (NSC-) based tumor-targeted gene therapy showed that NSC vectors expressing an artificially\nengineered viral fusogenic protein, VSV-G H162R, could cause tumor cell death specifically under acidic tumor microenvironment\nby syncytia formation; however, the killing efficiency still had much room to improve. In the view that coexpression of another\nantitumoral gene with VSV-G can augment the bystander effect, a synthetic regulatory system that triggers transgene expression\nin a cell fusion-inducible manner has been proposed. Here we have developed a double-switch cell fusion-inducible transgene\nexpression system (DoFIT) to drive transgene expression upon VSV-G-mediated NSC-glioma cell fusion. In this binary system,\ntransgene expression is coregulated by a glioma-specific promoter and targeting sequences of a microRNA (miR) that is highly\nexpressed in NSCs but lowly expressed in glioma cells.Thus, transgene expression is ââ?¬Å?switched offââ?¬Â by the miR in NSC vectors, but\nafter cell fusionwith glioma cells, the miR is diluted and loses its suppressive effect.Meanwhile, in the syncytia, transgene expression\nis ââ?¬Å?switched onââ?¬Â by the glioma-specific promoter. Our in vitro and in vivo experimental data show that DoFIT successfully abolishes\nluciferase reporter gene expression in NSC vectors but activates it specifically after VSV-G-mediated NSC-glioma cell fusion....
In gene therapy for congenital disorders, treatments during neonate and infant stages are promising. Replication-incompetent\nadenovirus (Ad) vectors have been used in gene therapy studies of genetic disorders; however, the transduction properties of Ad\nvectors in neonates and infants have not been fully examined. Accordingly, this study examined the properties of Ad vectormediated\ntransduction in neonatal mice. A first-generation Ad vector containing a cytomegalovirus (CMV) promoter-driven\nluciferase expression cassette was administered to neonatal mice on the second day of life via retro-orbital sinus. The highest Ad\nvector genome copy numbers and transgene expression were found in the neonatal liver.The neonatal heart exhibited the second\nhighest levels of transgene expression among the organs examined. There was an approximately 1500-fold difference in the transgene\nexpression levels between the adult liver and heart, while the neonatal liver exhibited only an approximately 30-fold higher level\nof transgene expression than the neonatal heart. A liver-specific promoter for firefly luciferase expression conferred a more than\n100-fold higher luciferase expression in the liver relative to the other organs. No apparent hepatotoxicity was observed in neonatal\nmice following Ad vector administration.These findings should provide valuable information for gene therapy using Ad vectors in\nneonates and infants...
Age-related macular degeneration (AMD) is the leading cause of substantial and irreversible vision loss amongst elderly populations\nin industrialized countries. The advanced neovascular (or ââ?¬Å?wetââ?¬Â) form of the disease is responsible for severe and aggressive loss of\ncentral vision. Current treatments aim to seal off leaky blood vessels via laser therapy or to suppress vessel leakage and neovascular\ngrowth through intraocular injections of antibodies that target vascular endothelial growth factor (VEGF).However, the long-term\nsuccess of anti-VEGF therapy can be hampered by limitations such as low or variable efficacy, high frequency of administration\n(usually monthly), potentially serious side effects, and, most importantly, loss of efficacy with prolonged treatment. Gene transfer\nof endogenous antiangiogenic proteins is an alternative approach that has the potential to provide long-term suppression of\nneovascularization and/or excessive vascular leakage in the eye. Preclinical studies of gene transfer in a large animal model have\nprovided impressive preliminary results with a number of transgenes. In addition, a clinical trial in patients suffering fromadvanced\nneovascular AMD has provided proof-of-concept for successful gene transfer. In this mini review, we summarize current theories\npertaining to the application of gene therapy for neovascular AMD and the potential benefits when used in conjunction with\nendogenous antiangiogenic proteins....
Today, nanotechnology plays a vital role in biomedical applications, especially for the diagnosis and treatment of various diseases.\nAmong the many different types of fabricated nanoparticles, magnetic metal oxide nanoparticles stand out as unique and useful\ntools for biomedical applications, because of their imaging characteristics and therapeutic properties such as drug and gene\ncarriers. Polymer-coated magnetic particles are currently of particular interest to investigators in the fields of nanobiomedicine\nand fundamental biomaterials. The ranostic magnetic nanoparticles that are encapsulated or coated with polymers not only exhibit\nimaging properties in response to stimuli, but also can efficiently deliver various drugs and therapeutic genes. Even though a large\nnumber of polymer-coated magnetic nanoparticles have been fabricated over the last decade,most of these have only been used for\nimaging purposes. The focus of this review is on polysaccharide-coated magnetic nanoparticles used for imaging and gene delivery....
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