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      Bioengineering Strategies for Protein-Based Nanoparticles

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          Abstract

          In recent years, the practical application of protein-based nanoparticles (PNPs) has expanded rapidly into areas like drug delivery, vaccine development, and biocatalysis. PNPs possess unique features that make them attractive as potential platforms for a variety of nanobiotechnological applications. They self-assemble from multiple protein subunits into hollow monodisperse structures; they are highly stable, biocompatible, and biodegradable; and their external components and encapsulation properties can be readily manipulated by chemical or genetic strategies. Moreover, their complex and perfect symmetry have motivated researchers to mimic their properties in order to create de novo protein assemblies. This review focuses on recent advances in the bioengineering and bioconjugation of PNPs and the implementation of synthetic biology concepts to exploit and enhance PNP’s intrinsic properties and to impart them with novel functionalities.

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          Most cited references209

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          Nanoparticle-based targeted drug delivery.

          Nanotechnology could be defined as the technology that has allowed for the control, manipulation, study, and manufacture of structures and devices in the "nanometer" size range. These nano-sized objects, e.g., "nanoparticles", take on novel properties and functions that differ markedly from those seen from items made of identical materials. The small size, customized surface, improved solubility, and multi-functionality of nanoparticles will continue to open many doors and create new biomedical applications. Indeed, the novel properties of nanoparticles offer the ability to interact with complex cellular functions in new ways. This rapidly growing field requires cross-disciplinary research and provides opportunities to design and develop multifunctional devices that can target, diagnose, and treat devastating diseases such as cancer. This article presents an overview of nanotechnology for the biologist and discusses the attributes of our novel XPclad((c)) nanoparticle formulation that has shown efficacy in treating solid tumors, single dose vaccination, and oral delivery of therapeutic proteins.
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            The coming of age of de novo protein design.

            There are 20(200) possible amino-acid sequences for a 200-residue protein, of which the natural evolutionary process has sampled only an infinitesimal subset. De novo protein design explores the full sequence space, guided by the physical principles that underlie protein folding. Computational methodology has advanced to the point that a wide range of structures can be designed from scratch with atomic-level accuracy. Almost all protein engineering so far has involved the modification of naturally occurring proteins; it should now be possible to design new functional proteins from the ground up to tackle current challenges in biomedicine and nanotechnology.
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              Self-assembling influenza nanoparticle vaccines elicit broadly neutralizing H1N1 antibodies.

              Influenza viruses pose a significant threat to the public and are a burden on global health systems. Each year, influenza vaccines must be rapidly produced to match circulating viruses, a process constrained by dated technology and vulnerable to unexpected strains emerging from humans and animal reservoirs. Here we use knowledge of protein structure to design self-assembling nanoparticles that elicit broader and more potent immunity than traditional influenza vaccines. The viral haemagglutinin was genetically fused to ferritin, a protein that naturally forms nanoparticles composed of 24 identical polypeptides. Haemagglutinin was inserted at the interface of adjacent subunits so that it spontaneously assembled and generated eight trimeric viral spikes on its surface. Immunization with this influenza nanoparticle vaccine elicited haemagglutination inhibition antibody titres more than tenfold higher than those from the licensed inactivated vaccine. Furthermore, it elicited neutralizing antibodies to two highly conserved vulnerable haemagglutinin structures that are targets of universal vaccines: the stem and the receptor binding site on the head. Antibodies elicited by a 1999 haemagglutinin-nanoparticle vaccine neutralized H1N1 viruses from 1934 to 2007 and protected ferrets from an unmatched 2007 H1N1 virus challenge. This structure-based, self-assembling synthetic nanoparticle vaccine improves the potency and breadth of influenza virus immunity, and it provides a foundation for building broader vaccine protection against emerging influenza viruses and other pathogens.
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                Author and article information

                Journal
                Genes (Basel)
                Genes (Basel)
                genes
                Genes
                MDPI
                2073-4425
                23 July 2018
                July 2018
                : 9
                : 7
                : 370
                Affiliations
                [1 ]Department of Molecular Sciences, Macquarie University, Sydney, NSW 2109, Australia; dennis.diaz-rincon@ 123456hdr.mq.edu.au (D.D.); andrew.care@ 123456mq.edu.au (A.C.)
                [2 ]Australian Research Council Centre of Excellence for Nanoscale BioPhotonics, Macquarie University, Sydney, NSW 2109, Australia
                [3 ]Biomolecular Discovery and Design Research Centre, Macquarie University, Sydney, NSW 2109, Australia
                Author notes
                [* ]Correspondence: anwar.sunna@ 123456mq.edu.au ; Tel.: +61-2-9850-4220
                Author information
                https://orcid.org/0000-0002-0035-7961
                https://orcid.org/0000-0002-1467-9937
                Article
                genes-09-00370
                10.3390/genes9070370
                6071185
                30041491
                aa4809cb-4c2c-4d7a-b853-b4eb951f358d
                © 2018 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 07 June 2018
                : 17 July 2018
                Categories
                Review

                protein-based nanoparticles,bioengineering,nanobiotechnology,synthetic biology,biomedicine,biocatalysis,virus-like particle,nanocages

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