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Strategies to Accomplish Targeted Gene Delivery Employing Tropism-Modified Adenoviral Vectors
Published in Kenneth L. Brigham, Gene Therapy for Diseases of the Lung, 2020
Joanne T. Douglas, David T. Curiel
Similar pseudotyping experiments have been performed with ecotropic Moloney murine leukemia virus (MoMLV). Preliminary work demonstrated that it was possible to assemble virions in which the genome of ecotropic MoMLV was encapsidated by the envelope protein of a related murine amphotropic retrovirus (22). The resultant virions were able to infect a wider range of host cells than those normally susceptible to MoMLV. Further work by this group resulted in the formation of pseudotyped MoMLV virions with alternative envelope glycoproteins derived from gibbon ape leukemia virus, human T-cell leukemia virus, or vesicular stomatitis virus (22,23). Once again, this approach was shown to be of utility in extending the host range of MoMLV to cells that are normally resistant to infection by this retrovirus. However, the targeting specificity of pseudotyped retrovirions is still limited to cells defined by the host range of the virus supplying the envelope glycoproteins.
Multiple Sclerosis
Published in Irun R. Cohen, Perspectives on Autoimmunity, 2020
The picture which emerges from this discussion is that of a slowly increasing number of foci in the MS patient’s CNS of proliferating T-cells, with a limited range of specifications (oligoclonal?) driven by the presence of astrocytic MHC antigens and resembling multiple disseminated lymphocytic tumor metastases. Such a picture agrees with recent imaging studies which suggest that MS lesions persist and grow larger over time. One is reminded of the essential role of murine leukemia virus in driving the continued proliferation within the thymus of T-lymphoma cells bearing receptors for the virus.235 Mutation and selection over a period of years would favor cells best fitted to continue proliferating in the CNS environment. The possibility must also be considered that suppressor cells cannot penetrate the CNS and that the hypothesized clonal proliferation would be free of the normal control exerted by such cells.
Acute and Chronic Transforming Retroviruses
Published in Pimentel Enrique, Oncogenes, 2020
Acute transforming retroviruses have been isolated from tumors occurring in different animal species but are not involved in a natural transmission of the diseases from one animal to another. For example, one of these viruses, the Harvey murine sarcoma virus (H-MuSV), was isolated from solid tumors that developed in rats previously injected with a chronic transforming retrovirus, the Moloney leukemia virus (M-MuLV).5 Presumably, this virus picked up genetic information from the rat cells in which M-MuLV had been propagated. By a similar procedure, a closely related retrovirus with acute transforming properties was isolated thereafter and was called K-MuSV.6 Another acute retrovirus, the Abelson murine leukemia virus (A-MuLV), arose in a steroid-treated mouse infected with M-MuLV,7 probably as a consequence of recombination of M-MuLV with cellular sequences.
Mechanisms of cellular and humoral immunity through the lens of VLP-based vaccines
Published in Expert Review of Vaccines, 2022
Hunter McFall-Boegeman, Xuefei Huang
Besides adding adjuvants that activate the entire immune response, with the concern of potentially severe over-activation, there has been work on engineering VLPs to activate only one type of immune cells. Because of their large size, VLPs drain from the site of infection into the lymphatic system and end up in the draining lymph nodes[98,99]. This is part of what makes them excellent at eliciting strong humoral responses. It also can be advantageous for cellular immunity, as naïve T cells are located in the paracortex along with DCs[100]. There, VLPs that display activation ligands for co-stimulatory receptors on T cells can bind their cognate receptors boosting activation and differentiation. Derdak et al. showed that Moloney murine leukemia virus (MoMLV) VLPs decorated with a TCR/CD3 ligand, CD80, and ICAM-1 can cause differentiation in T cells without the help of APCs[101]. Further experiments showed that the replacement of TCR/CD3 ligand with MHC class I molecules containing preprocessed antigens, can elicit antigen specific T cell responses. Although highly intriguing, this approach is specific to the VLP used.
Zinc ferrate nanoparticles for applications in medicine: synthesis, physicochemical properties, regulation of macrophage functions, and in vivo safety evaluation
Published in Nanotoxicology, 2020
Yu Wang, Yajie Liu, Jiajia Li, Xiaoqing Xu, Xinru Li
The murine macrophage (RAW 264.7) cells (passage no. 6), derived from tumors of BLAB/c mouse induced by Abelson murine leukemia virus, were purchased from Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences. As a sensitive and appropriate in vitro model, this cell line was applied in studying effects of NPs on cellular processes or functions such as in vitro cytotoxicity, intracellular localization of NPs, expression of cytokine, surface markers as well as ROS, phagocytic function, and so forth (Park et al. 2011; Nishanth et al. 2011). The cells were cultured in Dulbecco’s Modified Eagle’s medium (DMEM), supplemented with 100 U/mL penicillin, 100 μg/mL streptomycin, and 10% fetal bovine serum at 37 °C in a humidified atmosphere containing 5% CO2.
A tool with many applications: vesicular stomatitis virus in research and medicine
Published in Expert Opinion on Biological Therapy, 2020
Altar M. Munis, Emma M. Bentley, Yasuhiro Takeuchi
Gene therapy was born with the use of Moloney murine leukemia virus (MoMLV) based oncoretroviral vectors to deliver genetic payloads into target cells [51]. LVs were later designed by genetically modifying the HIV-1 genome and providing the necessary structural proteins in trans (reviewed in [52]). Overall, LV is currently the vector of choice for many gene therapy applications, in particular ex vivo cell therapies, due to their high carrying capacity, ability to be pseudotyped with heterologous envelopes, increased biosafety owing to the generation of self-inactivating vectors, integration into the host genome allowing for sustained transgene expression, and arguably lower immunogenicity of viral proteins. The choice of envelope used to pseudotype LVs dictates various properties of the vector including cell tropism, serum sensitivity, physical, and thermostability.