Current Issue : July - September Volume : 2016 Issue Number : 3 Articles : 4 Articles
Due to the increasing amount of people afflicted worldwide with Chagas disease and\nan increasing prevalence in the United States, there is a greater need to develop a safe and effective\nvaccine for this neglected disease. Adenovirus serotype 5 (Ad5) is the most common adenovirus\nvector used for gene therapy and vaccine approaches, but its efficacy is limited by preexisting\nvector immunity in humans resulting from natural infections. Therefore, we have employed rare\nserotype adenovirus 48 (Ad48) as an alternative choice for adenovirus/Chagas vaccine therapy.\nIn this study, we modified Ad5 and Ad48 vectors to contain T. cruziââ?¬â?¢s amastigote surface protein\n2 (ASP-2) in the adenoviral early gene. We also modified Ad5 and Ad48 vectors to utilize the\nââ?¬Å?Antigen Capsid-Incorporationââ?¬Â strategy by adding T. cruzi epitopes to protein IX (pIX). Mice that\nwere immunized with the modified vectors were able to elicit T. cruzi-specific humoral and cellular\nresponses. This study indicates that Ad48-modified vectors function comparable to or even premium\nto Ad5-modified vectors. This study provides novel data demonstrating that Ad48 can be used as\na potential adenovirus vaccine vector against Chagas disease....
Colorectal cancer (CRC) metastatic dissemination to the liver is one\nof the most life-threatening malignancies in humans and represents\nthe leading cause of CRC-related mortality. Herein, we adopted a\ngene transfer strategy into mouse hematopoietic stem/progenitor\ncells to generate immune-competent mice in which TEMsââ?¬â?a subset\nof Tie2+ monocytes/macrophages found at peritumoral sitesââ?¬â?\nexpress interferon-alpha (IFNa), a pleiotropic cytokine with antitumor\neffects. Utilizing this strategy in mouse models of CRC liver\nmetastasis, we show that TEMs accumulate in the proximity of\nhepatic metastatic areas and that TEM-mediated delivery of IFNa\ninhibits tumor growth when administered prior to metastasis challenge\nas well as on established hepatic lesions, improving overall\nsurvival. Further analyses unveiled that local delivery of IFNa does\nnot inhibit homing but limits the early phases of hepatic CRC cell\nexpansion by acting on the radio-resistant hepatic microenvironment.\nTEM-mediated IFNa expression was not associated with\nsystemic side effects, hematopoietic toxicity, or inability to respond\nto a virus challenge. Along with the notion that TEMs were detected\nin the proximity of CRC metastases in human livers, these results\nraise the possibility to employ similar gene/cell therapies as tumor\nsite-specific drug-delivery strategies in patients with CRC....
The goal of magnetic field-assisted gene transfer is to enhance internalization of exogenous nucleic acids by association with magnetic nanoparticles (MNPs). This technique named magnetofection is particularly useful in difficultto- transfect cells. It is well known that human, mouse, and rat skeletal muscle cells suffer a maturation-dependent loss of susceptibility to Recombinant Adenoviral vector (RAd) uptake. In postnatal, fully differentiated myofibers, the expression of the primary Coxsackie and Adenoviral membrane receptor (CAR) is severely downregulated representing a main hurdle for the use of these vectors in gene transfer/therapy. Here we demonstrate that assembling of Recombinant Adenoviral vectors with suitable iron oxide MNPs into magneto-adenovectors (RAd-MNP) and further exposure to a gradient magnetic field enables to efficiently overcome transduction resistance in skeletal muscle cells. Expression of Green Fluorescent Protein and Insulin-like Growth Factor 1 was significantly enhanced after magnetofection with RAd-MNPs complexes in C2C12 myotubes in vitro and mouse skeletal muscle in vivo when compared to transduction with naked virus. These results provide evidence that magnetofection, mainly due to its membrane-receptor independent mechanism, constitutes a simple and effective alternative to current methods for gene transfer into traditionally hard-to-transfect biological models....
Gene delivery systems can be divided to two major types: vector-based (either viral\nvector or non-viral vector) and physical delivery technologies. Many physical carriers,\nsuch as electroporation, gene gun, ultrasound start to be proved to have the potential\nto enable gene therapy. A relatively new physical delivery technology for gene delivery\nconsists of microneedles (MNs), which has been studied in many fields and for many\nmolecule types and indications. Microneedles can penetrate the stratum corneum, which\nis the main barrier for drug delivery through the skin with ease of administration and\nwithout significant pain. Many different kinds of MNs, such as metal MNs, coated MNs,\ndissolving MNs have turned out to be promising in gene delivery. In this review, we\ndiscussed the potential as well as the challenges of utilizing MNs to deliver nucleic acids\nfor gene therapy. We also proposed that a combination of MNs and other gene delivery\napproaches may lead to a better delivery system for gene therapy....
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