Advances in the Development of Virus-Like Particles as Tools in Medicine and Nanoscience

Abstract

Virus-like particles (VLPs) are viral coats formed by the self-assembly of the components of viruses excluding their genetic material. These particles may be used as vectors to transport molecules chemically attached on the VLP surface, or as vessels for the systemic delivery of pharmacologically important molecules as drugs, siRNAs, genes, mRNAs, magnetic nanoparticles, quantum dots and other medical-imaging aids. Herein we review the recent advances in heterologous production and purification of VLPs, the current trends in chemical modification of VLPs, and the advances on the application of VLPs as vectors, tools for medical imaging and materials for nanotechnology.

The Last Ten Years of Advancements in Plant-Derived Recombinant Vaccines against Hepatitis B

“…Several reports on the expression of properly assembled VLPs at adequate levels have been published for the influenza virus [24], human papillomavirus [25], human immunodeficiency virus [26,27], Norwalk virus [28], and hepatitis B virus [26,29,30]. In recent, VLPs have been applied in various fields, not only as vaccines [31,32] but also as delivery agents for therapeutic medicine [33,34,35,36]. In addition, Paul et al [37] summarized four major developments of molecular pharmaceuticals occurring in the world.…”

Engineered Biological Entities for Drug Delivery and Gene Therapy

“…Some of these properties such as cellular tropism and uptake, intracellular trafficking, membrane translocation, and transfer of nucleic acids or molecules across the cytoplasmic, endosomal, and nuclear membranes are important for drug delivery and gene therapy. 120,153,155,[158][159][160] Usually, the degree of similarity of VLPs and their viruses depends on the number of proteins incorporated into the constructs. 161,162 Since the first description in 1983 of the viral DNA packaging into mouse polyomavirus (MPyV) VLPs and its transduction in vitro, 163 VLPs of different viruses such as papillomaviruses, [164][165][166] hepatitis B, C, and E viruses, [167][168][169] polyomaviruses, 163,[170][171][172][173][174][175][176][177][178][179] lentivirus, 180,181 rotavirus, 145,182 parvovirus, 183,184 and norovirus 185 have been generated.…”

“…[190][191][192][193] On the other hand, VLPs are considered biologically safe nanostructures since they are not infectious (lack of viral genome) and do not replicate, representing a safer alternative to viral vectors. 160,[194][195][196][197] However, they can elicit immune and inflammatory responses, especially when repeated administration is needed. 152 It has to be also noted that when used in vaccination, VLPs could show excellent adjuvant properties and the majority of VLPs stimulate strong cellular and humoral immune responses as direct immunogens.…”

“…198 It has been suggested that recombinant VLPs derived from infection of insect cells with baculovirus or even those derived from prokaryotic systems could be contaminated with different residual components of these host cells, contributing those impurities to the adjuvant properties. 153 One interesting property of VLPs is that coat viral proteins present an enormous elasticity and adaptability to be modified chemically and/or by protein genetic engineering 154,160,199 to incorporate multiple directed functionalities, in order to be addressed in biomedical applications such as drug delivery or gene therapy. It has been recently reviewed that chemically and/or genetically modified VLPs, including CPMV, CCMV, MS2, M13 bacteriophages, and other virus-based nanoparticles, 155,186 could maintain their structural integrity and improve their physical stability 154 and, moreover, these modifications could also confer desired cell-targeting properties to the nanovehicle.…”

“…152,195 As described above, VLPs can be used as empty nanocarriers to transport molecules chemically attached on their surface or can be loaded ex vivo with therapeutic small molecules such as drugs, DNAs, mRNAs, siRNAs, oligonucleotides, quantum dots, magnetic nanoparticles, or proteins. 155,157,160 VLPs of different papillomavirus and polyomavirus have been widely characterized and used for directed delivery in biomedical applications. 132,165,173,174,194,202 Osmotic shock and in vitro self-assembling of VLP subunits in the presence of 266 the cargo have been the two main strategies used to packaged nucleic acid or other small molecules.…”