Current Issue : October - December Volume : 2014 Issue Number : 4 Articles : 6 Articles
Recent success in the treatment of congenital blindness demonstrates the potential of ocular gene therapy as a therapeutic approach.\nThe eye is a good target due to its small size, minimal diffusion of therapeutic agent to the systemic circulation, and low immune\nand inflammatory responses. Currently, most approaches are based on viral vectors, but efforts continue towards the synthesis and\nevaluation of new nonviral carriers to improve nucleic acid delivery. Our objective is to evaluate the efficiency of novel cationic\nretinoic and carotenoic glycol phospholipids, designated C20-18, C20-20, and C30-20, to deliver DNA to human retinal pigmented\nepithelium (RPE) cells. Liposomes were produced by solvent evaporation of ethanolic mixtures of the polyene compounds\nand coformulated with 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) or cholesterol (Chol). Addition of DNA to the\nliposomes formed lipoplexes, which were characterized for binding, size, biocompatibility, and transgene efficiency. Lipoplex\nformulations of suitable size and biocompatibility were assayed for DNA delivery, both qualitatively and quantitatively, using RPE\ncells and a GFP-encoding plasmid.The retinoic lipoplex formulation with DOPE revealed a transfection efficiency comparable to\nthe known lipid references 3????-[N-(N????,N????-dimethylaminoethane)-carbamoyl]-cholesterol (DC-Chol) and 1,2-dioleoyl-sn-glycero-\n3-ethylphosphocholine (EPC) and GeneJuice. The results demonstrate that cationic polyene phospholipids have potential as DNA\ncarriers for ocular gene therapy....
Existing nonviral gene delivery systems to lungs are inefficient and associated with dose limiting toxicity in mammalian cells.\nTherefore, carbonate apatite (CO3Ap) nanoparticles were examined as an alternative strategy for effective gene delivery to the\nlungs. This study aimed to (1) assess the gene delivery efficiency of CO3Ap in vitro and inmouse lungs, (2) evaluate the cytotoxicity\neffect of CO3Ap/pDNA in vitro, and (3) characterize the CO3Ap/pDNA complex formulations. A significantly high level of reporter\ngene expression was detected from the lung cell line transfected with CO3Ap/pDNA complex prepared in both serum and serumfree\nmedium. Cytotoxicity analysis revealed that the percentage of the viable cells treated with CO3Ap to be almost similar to the\nuntreated cells. Characterization analyses showed that the CO3Ap/pDNA complexes are in a nanometer range with aggregated\nspherical structures and tended to be more negatively charged. In the lung of mice, highest level of transgene expression was\nobserved when CO3Ap (8 ????L) was complexed with 40 ????g of pDNA at day 1 after administration. Although massive reduction of\ngene expression was seen beyond day 1 post administration, the level of expression remained significant throughout the study\nperiod....
Gene therapy and cell-based therapy have emerged as novel therapies to promote therapeutic angiogenesis in critical limb ischemia\n(CLI) caused by peripheral artery disease (PAD). Although researchers initially focused on gene therapy using proangiogenic\nfactors, such as vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), and hepatocyte growth factors (HGF),\ncell therapy using bone marrow mononuclear cells (BMMNCs), mesenchymal stem cells (BMMSCs), G-CSF-mobilized peripheral\nblood mononuclear cells (M-PBMNCs), and endothelial progenitor cells (EPCs) have also been extensively studied. Based on\nthe elaborate studies and favorable results of basic research, some clinical phase I/II trials have been performed, and the results\ndemonstrate the safety of these approaches and their potential for symptomatic improvement in CLI. However, the phase 3 clinical\ntrials have thus far been limited to gene therapy using the HGF gene. Further studies using well-designed larger placebo-controlled\nand long-term randomized control trials (RCTs) will clarify the effectiveness of gene therapy and cell-based therapy for the\ntreatment of CLI. Furthermore, the development of efficient gene transfer systems and effective methods for keeping transplanted\ncells healthy will make these novel therapies more effective and ease the symptoms of CLI....
Angiogenesis plays a vital part in the pathogenesis and treatment of cardiovascular disease and has become one of the hotspots that\nare being discussed in the past decades. At present, the promising angiogenesis therapies are gene therapy and stem cell therapy.\nBesides, a series of studies have shown that the ultrasound targeted microbubble destruction (UTMD) was a novel gene delivery\nsystem, due to its advantages of noninvasiveness, low immunogenicity and toxicity, repeatability and temporal and spatial target\nspecificity; UTMD has also been used for angiogenesis therapy of cardiovascular disease. In this review, we mainly discuss the\ncombination of UTMD and gene therapy or stem cell therapy which is applied in angiogenesis therapy in recent researches, and\noutline the future challenges and good prospects of these approaches...
Proteins and genes of therapeutic interests in conjunction with different delivery systems are growing towards new heights. ââ?¬Å?Next\ngeneration delivery systemsââ?¬Â may providemore efficient platformfor delivery of proteins and genes. In the present review, snapshots\nabout the benefits of proteins or gene therapy, general procedures for therapeutic protein or gene delivery system, and different next\ngeneration delivery system such as liposome, PEGylation, HESylation, and nanoparticle based delivery have been depicted with\ntheir detailed explanation....
Current prostate cancer treatment, especially hormone refractory cancer, may create profound iatrogenic outcomes because of the\nadverse effects of cytotoxic agents. Suicide gene therapy has been investigated for the substitutemodality for current chemotherapy\nbecause it enables the treatment targeting the cancer cells. However the classic suicide gene therapy has several profound side\neffects, including immune-compromised due to viral vector. Recently, stem cells have been regarded as a new upgraded cellular\nvehicle or vector because of its homing effects. Suicide gene therapy using genetically engineered mesenchymal stem cells or neural\nstem cells has the advantage of being safe, because prodrug administration not only eliminates tumor cells but consequently kills\nthemore resistant therapeutic stem cells as well.The attractiveness of prodrug cancer gene therapy by stem cells targeted to tumors\nlies in activating the prodrug directly within the tumor mass, thus avoiding systemic toxicity. Therapeutic achievements using\nstem cells in prostate cancer include the cytosine deaminase/5-fluorocytosine prodrug system, herpes simplex virus thymidine\nkinase/ganciclovir, carboxyl esterase/CPT11, and interferon-beta. The aimof this study is to review the stem cell therapy in prostate\ncancer including its proven mechanisms and also limitations....
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