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Structure-based design and experimental engineering of a plant virus nanoparticle for the presentation of immunogenic epitopes and as a drug carrier

TitoloStructure-based design and experimental engineering of a plant virus nanoparticle for the presentation of immunogenic epitopes and as a drug carrier
Tipo di pubblicazioneArticolo su Rivista peer-reviewed
Anno di Pubblicazione2014
AutoriArcangeli, Caterina, Circelli P., Donini Marcello, Aljabali A.A.A., Benvenuto Eugenio, Lomonossoff G.P., and Marusic Carla
RivistaJournal of Biomolecular Structure and Dynamics
Volume32
Paginazione630-647
ISSN07391102
Parole chiaveAmino Acid Sequence, antineoplastic agent, artichoke mottled crinkle virus, article, chimera, computer model, controlled study, drug carrier, Drug Carriers, Drug Design, drug safety, drug structure, epitope mapping, Epitopes, gene insertion, gene structure, Genetic engineering, HIV-1, Human immunodeficiency virus, Humans, immunogenicity, Models, Molecular, molecular dynamics, Molecular Sequence Data, monoclonal antibody 2F5, nanoparticle, Nanoparticles, nonhuman, plant virus, Plant Viruses, priority journal, Protein Conformation, Sequence Alignment, sequence homology, structure analysis, Structure-Activity Relationship, Tombusvirus, vaccination, viral gene delivery system, Viral Proteins, virus capsid, virus like agent
Abstract

Biomaterials research for the discovery of new generation nanoparticles is one of the most active areas of nanotechnoloy. In the search of nature-made nanometer-sized objects, plant virus particles appear as symmetrically defined entities that can be formed by protein self-assembly. In particular, in the field of plant virology, there is plenty of literature available describing the exploitation of plant viral cages to produce safe vaccine vehicles and nanoparticles for drug delivery. In this context, we have investigated on the use of the artichoke mottled crinkle virus (AMCV) capsid both as a carrier of immunogenic epitopes and for the delivery of anticancer molecules. A dual approach that combines both in silico tools and experimental virology was applied for the rational design of immunologically active chimeric virus-like particles (VLPs) carrying immunogenic peptides. The atomic structures of wild type (wt) and chimeric VLPs were obtained by homology modeling. The effects of insertion of the HIV-1 2F5 neutralizing epitope on the structural stability of chimeric VLPs were predicted and assessed by detailed inspection of the nanoparticle intersubunit interactions at atomic level. Wt and chimeric VLPs, exposing on their surface the 2F5 epitope, were successfully produced in plants. In addition, we demonstrated that AMCV capsids could also function as drug delivery vehicles able to load the chemotherapeutic drug doxorubicin. To our knowledge, this is the first systematic predictive and empirical research addressing the question of how this icosahedral virus can be used for the production of both VLPs and viral nanoparticles for biomedical applications. © 2013 Taylor & Francis.

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cited By 11

URLhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-84892992911&doi=10.1080%2f07391102.2013.785920&partnerID=40&md5=5a3a10ee85a04f5e6b10ebfe8246098d
DOI10.1080/07391102.2013.785920
Citation KeyArcangeli2014630