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Conditional Replication of Oncolytic Virus Based on Detection of Oncogenic mRNA
Published in Yashwant V. Pathak, Gene Delivery Systems, 2022
Rakesh Sharma, Arvind Trivedi, Robert Moffatt
Oncolytic viruses are replicating microorganisms that have been selected or engineered to grow inside tumor cells. Oncolytic viruses specifically target cancer cells because they are able to exploit the very same cellular defects that promote tumor growth. These oncolytic viruses initially were viewed with skepticism for virus therapies. Virus therapy concept emerged based on tumor-specific mutations, including genetically engineered for specific signaling pathways or transcription activation programs and restricted virus entry in tumor cells (antigens overexpressed on the tumor cell surface) to kill tumor cells by oncolytic virus by cellular translational and transcriptional machinery, were discovered ultimately to induce cell necrosis or apoptosis. In the last decade, patients were treated in the first bona fide clinical trials of oncolytic virus therapy after a few valid phase I or II clinical trials and a single published ONYX-015 phase III incomplete trial. So clinical experience is limited to optimize the efficacy of certain oncolytic viruses: vaccinia virus, adenovirus, reovirus, Newcastle disease virus (NDV), coxsackie virus and herpes simplex virus (HSV).
Artificial Nanomachines and Nanorobotics
Published in Shaker A. Mousa, Raj Bawa, Gerald F. Audette, The Road from Nanomedicine to Precision Medicine, 2020
Alexandre Loukanov, Hristo Gagov, Seiichiro Nakabayashi
Biologically inspired nanorobots are known as bionanorobots. This is another research field for the development of nanorobotics by creation of artificial biological systems—both engineered viruses and bacteria. These so-called microbiological bionanorobots are able to implement a dozen or so important functions with medical application in oncology. The engineered viruses are used in experimental genetic therapies as devices for the transportation of anticancer drugs, salts, nucleic acids, and other molecules; repairing damage; and replicating DNA [31]. The oncolytic viruses that are highly specific against cancer cells open new medical approaches in antitumor therapies. The engineered bacteria are able to avoid potential immune response, to manufacture cellular biomolecules and to produce anticancer proteins that can shrink tumors. The nanorobotics bacteria are capable of navigating through the bloodstream and thus targeting the tumor cells throughout the body.
Aptamers as Tools for Targeted Drug Delivery
Published in Rakesh N. Veedu, Aptamers, 2017
Two RNA aptamers, D-12 and D-26, which target the hemagglutinin protein of influenza virus, were selected to test the therapeutic activity against influenza [34]. In influenza virus, the hemagglutinin protein mediates the initial steps in viral infection–receptor (glycan) binding and membrane fusion for cell entry. Both the aptamers were found to interfere with hemagglutinin–glycan interaction. The D-26 aptamer showed higher efficiency in distinguishing viral strains, and the affinity was further improved by incorporating the aptamer with 2′-fluoropyrimidines [34]. Oncolytic viruses are tumor-selective viruses that can destroy cancer cells by oncolysis. But quick clearance from the bloodstream and the acquired immunity to repeated infections by neutralizing antibodies (nAbs) restricts the use of oncolytic viruses in therapeutic applications. In a novel and versatile approach called aptamer-facilitated virus protection (AptaVIP), two types of aptamers were raised by the modified SELEX method to increase the in vivo oncolytic viral survival as a mode of anticancer treatment [57]. DNA aptamers were selected against vesicular stomatitis virus (oncolytic virus) and against the antigen-binding fragment (Fab) of antivesicular stomatitis virus polyclonal antibodies for shielding and blocking purposes, respectively, and they were modified and bridged together to form tetrameric counterparts. The authors were successful in demonstrating the use of this dual-aptamer AptaVIP system to block the antiviral antibodies and shield the virus from antibody neutralization that resulted in 77% viral infectivity in plaque-forming assay [57].
Modelling combined virotherapy and immunotherapy: strengthening the antitumour immune response mediated by IL-12 and GM-CSF expression
Published in Letters in Biomathematics, 2018
Adrianne L. Jenner, Chae-Ok Yun, Arum Yoon, Adelle C. F. Coster, Peter S. Kim
While the cytotoxic effects of viruses are most commonly viewed in terms of pathogenicity, it is possible to harness their activity for therapeutic purposes. Oncolytic viruses are genetically engineered viruses that selectively infect, self-replicate and lyse cancer cells (Parato, Senger, Forsyth, & Bell, 2005). They may be fortuitously tumour selective in wild-type; however, in most cases, attenuated forms are engineered to provide tumour selectivity. In this article, we will examine the usefulness of a gene-attenuated oncolytic adenovirus genetically engineered by Choi, Zhang, Choi, Kim, and Yun (2012a) to selectively infect and replicate within tumour cells and release the immunostimulatory cytokines interleukin 12 (IL-12) and granulocyte monocyte stimulating factor (GM-CSF). In this way, Choi et al. manufactured a virus that not only eradicates tumour cells, but also activates immune cells to do the same.
Treating cancerous cells with viruses: insights from a minimal model for oncolytic virotherapy
Published in Letters in Biomathematics, 2018
Adrianne L. Jenner, Adelle C. F. Coster, Peter S. Kim, Federico Frascoli
Interest in oncolytic virotherapy arises from its capacity to combine tumour-specific lysis with delivery properties for other anti-cancer drugs (Lawler et al., 2017). Oncolytic viruses are engineered to express genes that promote viral replication within tumour cells and inhibit replication within healthy cells. As such, the viral load remaining after the tumour cells have been eradicated will not affect the rest of the body and will decay over time. Once inside a tumour cell, virus particles will replicate until they reach a tumour-cell-filling capacity, at which point the cell will burst, undergoing lysis, and release the viral progeny inside. By replicating within tumour cells, oncolytic viruses are able to rapidly increase their population at the tumour site. This makes oncolytic virotherapy, in theory, a successful cancer treatment.
Tumour-associated macrophages and oncolytic virotherapies: a mathematical investigation into a complex dynamics
Published in Letters in Biomathematics, 2018
Oncolytic viruses (i.e. viruses that selectively replicate in, and destroy cancer cells) are emerging as an important approach in cancer treatment, due to their potential of inducing systemic anti-tumour immunity in addition to selectively killing cancer cells (Kaufman, Kolhapp, & Zloza, 2016). However, the effectiveness of these viruses – once they are injected into the patient – depends not only on the pathogenic nature of virally encoded genes, but also on the interactions between the virus and the host immune response, which might impact the ability of the virus to replicate (Kaufman et al., 2016).