Evaluation of the Nucleopolyhedrovirus of Anticarsia gemmatalis as a Vector for Gene Therapy in Mammals

Abstract

Background: Baculoviruses are insect pathogens with important biotechnological applications that transcend their use as biological controllers of agricultural pests. One species, Autographa californica multiple nucleopolhyedrovirus (AcMNPV) has been extensively exploited as a molecular platform to produce recombinant proteins and as a delivery vector for genes in mammals, because it can transduce a wide range of mammalian cells and tissues without replicating or producing progeny. Objective/Method: To investigate if the budded virions of Anticarsia gemmatalis multiple nucleopolhyedrovirus (AgMNPV) species has the same ability, the viral genome was modified by homologous recombination into susceptible insect cells to integrate reporter genes and then it was evaluated on mammalian cell lines in comparative form with respect to equivalent viruses derived from AcMNPV. Besides, the replicative capacity of AgMNPV´s virions in mammals was determined. Results: The experiments carried out showed that the recombinant variant of AgMNPV transduces and support the expression of delivered genes but not replicates in mammalian cells. Conclusion: Consequently, this insect pathogen is proposed as an alternative of non-infectious viruses in humans to explore new approaches in gene therapy and other applications based on the use of mammalian cells.

Solutions against emerging infectious and noninfectious human diseases through the application of baculovirus technologies

“…Because most of these pathogens have a very narrow host range, they depend on particular species of invertebrates for their natural sustenance (Rohrmann 2019). Baculoviruses do not infect vertebrates and although BVs have been found to be able to transduce cells from animals that are not their natural hosts-including mammals (Airenne et al 2011;Ono et al 2018;Parsza et al 2020)-viral DNA is unable to replicate and support progeny generation (Tija et al 1983;Kost and Condreay 2002;Parsza et al 2020). In fact, cell lines from mammals transduced with baculoviruses revealed Fig.…”

“…Later ODVs (Fig. 1C) were found to not possess this capability (Mäkelä et al 2008), with the result that the range of the baculovirus species sharing this characteristic was then expanded by adding studies about the BVs of Bombyx mori nucleopolyhedrovirus (Kenoutis et al 2006;Liu et al 2017) and the Anticarsia gemmatalis nucleopolyhedrivirus AgMNPV (Parsza et al 2020). In particular, these benefits in mammalian were reported to be due to the GP64 protein present in the BV envelopes of group 1-alphabaculoviruses (Kataoka et al 2012;Luz-Madrigal et al 2013); consequently narrowing down the feasibility of such applications to this specific subgroup of species, for which the viral entry mechanism would be based on clathrin-mediated endocytosis (Fujita et al 2006;Liu et al 2014;Hu et al 2019b).…”

Drug repositioning for SARS-CoV-2 by Gaussian kernel similarity bilinear matrix factorization

“…Wang et al predicted anti-SARS-COV-2 drugs by bound nuclear norm regularization ( Wang et al, 2021 ). Meng et al builded the human drug virus database and identified anti-SARS-COV-2 drugs by similarity constrained probabilistic matrix factorization ( Lu et al, 2021 ; Meng et al, 2021 ; Parsza et al, 2021 ). Shen et al prioritized anti-SARS-CoV-2 drugs by combining an unbalanced bi-random walk and Laplacian regularized least squares ( Shen et al, 2022 ).…”