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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
Thus, the capacity to achieve targeted, cell-specific gene delivery by modifications of viral tropism has been established by these studies which employed genetic, chemical and immunological approaches. It is thus logical to pursue strategies to modify the tropism of adenoviral vectors, which are of great utility for in vivo gene delivery. This would theoretically allow the derivation of a vector exhibiting both in vivo efficacy and cell-specificity, which are desirable features for pulmonary gene therapy applications.
Measles and its neurological complications
Published in Avindra Nath, Joseph R. Berger, Clinical Neurovirology, 2020
Benedikt Weissbrich, Jürgen Schneider-Schaulies
One of the most important characteristics determining viral tropism is the usage of specific receptors on the surface of susceptible target cells that allow viral attachment and penetration. MV is highly species specific in that it does not naturally replicate in nonprimate hosts. In vivo it reveals a pronounced tropism for cells of the hematopoietic lineage and epithelial cells. Multinucleated giant cells are formed in lymph nodes. They are pathognomonic for the measles infection. However, endothelial cells and neural cells such as neurons, astrocytes and microglial cells can also be infected. As cellular receptors for MV, the widely expressed transmembrane protein CD46 [12,13], the lymphoid cell specific signaling lymphocytic activation molecule (SLAM, CD150) [14,15], and the epithelial cell-specific receptor nectin-4 [16,17] have been identified. In contrast to CD46, which is utilized by vaccine and lab-adapted MV strains, all wild-type strains and isolates interact with CD150 on the surface of activated B and T cells, dendritic and memory cells, and with nectin-4 on epithelial cells.
Therapies to Prevent or Inhibit Chemokine Receptor Expression
Published in Thomas R. O’Brien, Chemokine Receptors and AIDS, 2019
J. Scott Cairns, M. Patricia D’Souza
The differential use of CCR5 and CXCR4 by HIV strains coupled with the expression patterns of these receptors in primary cells largely explains viral tropism. M-tropic or non-syncytium-inducing (NSI) viruses are designated R5 viruses since they utilize CCR5, a chemokine receptor present on CD4+ macrophages and CD4+ T lymphocytes (14–16). T-tropic or syncytium-inducing (SI) viruses utilize CXCR4 and are designated X4 viruses. CXCR4 is present on CD4+ T cell lines and many other types of primary human cells (17–19). Dual tropic strains of HIV are designated R5X4 since they are capable of infecting CD4+ macrophages and lymphocytes as well as immortalized CD4+ T cell lines that express both CCR5 and CXCR4 (20).
Immunobiology and nanotherapeutics of severe acute respiratory syndrome 2 (SARS-CoV-2): a current update
Published in Infectious Diseases, 2021
Ifeanyi Elibe Mba, Hyelnaya Cletus Sharndama, Goodness Ogechi Osondu-chuka, Onyekachi Philomena Okeke
A recent study led by Prof. Nan-Shan Zhong’s team, by sampling 1099 laboratory-confirmed cases, found that the common clinical manifestations included fever (88.7%), cough (67.8%), fatigue (38.1%), sputum production (33.4%), shortness of breath (18.6%), sore throat (13.9%), and headache (13.6%) [77]. A part of patients manifested gastrointestinal symptoms, with diarrhoea (3.8%) and vomiting (5.0%). The clinical manifestations were inconsistent with the previous data of 41, 99, and 138 patients’ analyses in Hubei province [28,80]. Fever and cough were the dominant symptoms, whereas upper respiratory signs and gastrointestinal symptoms were rare, suggesting the differences in viral tropism compared with SARS-CoV, MERS-CoV, and influenza [65]. The elderly and those with underlying disorders (i.e. hypertension, chronic obstructive pulmonary disease, diabetes, cardiovascular disease) developed rapidly into acute respiratory distress syndrome, septic shock, metabolic acidosis, and coagulation dysfunction, even leading to death [65]. Minor symptoms of SARS-CoV-2 that are often neglected but very important include dysgeusia [83], anosmia [84], and skin lesions [85].
Harnessing the power of foot-and-mouth-disease virus for targeting integrin alpha-v beta-6 for the therapy of cancer
Published in Expert Opinion on Drug Discovery, 2021
The idea of using viruses to selectively kill cancer cells has existed for decades, however in recent years there has been a surge of interest in re-targeting viral tropism to selectively target neoplastic cells. The purpose of an oncolytic virus is to selectively replicate only in cancer cells leading to cell death [36]. This also leads to a secondary response as the cells burst and the virus is released in to the tumor microenvironment, triggering an immune response. Adenoviruses are a well characterized family of viruses which are excellent candidates for use as an oncolytic virus as they are easily manipulated and genetically modified [36]. Table 2 summarizes the Ad5 variants that have incorporated A20FMDV2 to target αvβ6 as a component of their design.
The dawn of precision medicine in HIV: state of the art of pharmacotherapy
Published in Expert Opinion on Pharmacotherapy, 2018
Ying Mu, Sunitha Kodidela, Yujie Wang, Santosh Kumar, Theodore J. Cory
CCR5 antagonist test and HLA-B*5701 allele test are two other lab tests recommended by FDA for ART administration. Identifying the pharmacogenetics of patients’ is another way to apply for the precision medicine. Patients with the HLA-B*5701 allele are at a higher risk of hypersensitivity to react with abacavir. HLA-B*5701 screening is recommended prior to prescribing abacavir. GT of viral tropism is widely used in the clinical settings to test patient’s [171] dominant virus population. The genetic test of CYP2B6 516 G > T is useful to identify side effects of patients using efavirenz. UGT1A1*28 testing prior administration of ATV can reduce the risk of hyperbilirubinemia. These current tests in the clinic are essential to practice precision antiretrovirals. However, improvements are in need: patients’ genetic tests are not always available, and the tests can be costly and time consuming. Furthermore, drug response may be effected by multiple genes and not just the one code for the specific protein. These tests reduce the risk of side effects and improve drug efficacy, but going forward will require knowledge of genetic risk factors and the development of new DNA technologies. With advanced knowledge of the human genome and new technologies, including DNA microarrays, DNA chips, and human genome analysis, in the future patients’ specific gene characteristics will be basic information for physicians to choose drug combinations, optimizing drug concentration and minimizing the side effects.