Assembly, Engineering and Applications of Virus-Based Protein Nanoparticles

Abstract

Viruses and their protein capsids can be regarded as biologically evolved nanomachines able to perform multiple, complex biological functions through coordinated mechano-chemical actions during the infectious cycle. The advent of nanoscience and nanotechnology has opened up, in the last 10 years or so, a vast number of novel possibilities to exploit engineered viral capsids as protein-based nanoparticles for multiple biomedical, biotechnological or nanotechnological applications. This chapter attempts to provide a broad, updated overview on the self-assembly and engineering of virus capsids, and on applications of virus-based nanoparticles. Different sections provide outlines on: (i) the structure, functions and properties of virus capsids; (ii) general approaches for obtaining assembled virus particles; (iii) basic principles and events related to virus capsid self-assembly; (iv) genetic and chemical strategies for engineering virus particles; (v) some applications of engineered virus particles being developed; and (vi) some examples on the engineering of virus particles to modify their physical properties, in order to improve their suitability for different uses.

A molecular breadboard: Removal and replacement of subunits in a hepatitis B virus capsid

“…17 Properties of virus capsids, symmetry, selfassembly, and their container-like geometry have led to research to develop them as vehicles for nanotechnology. 18,19 Though capsids are built of many subunits, a key feature of modular construction, the ability to swap out components, has not to our knowledge been developed for capsids. In electronics, a breadboard is a chassis where components can readily be inserted and removed to test ciruit design.…”

Targeted delivery of 5-fluorouracil-1-acetic acid (5-FA) to cancer cells overexpressing epithelial growth factor receptor (EGFR) using virus-like nanoparticles

“…Over the past decade, delivery systems using nanoparticles, such as cationic liposomes, polymers, carbon nanotubes and virus-like nanoparticles (VLNPs) have been developed with the aim to improve therapeutic efficacies of anticancer drugs, while minimizing their undesirable side effects [15][16][17][18][19][20][21] . Among these nanoparticles, VLNPs demonstrate the potential for the delivery of a broad spectrum of chemotherapeutics, owing to their favorable characteristics, including (1) biocompatibility and biodegradability 22 , (2) homogeneity with specific compositions and molecular structures 23 , (3) self-assembling into nanoparticles with relatively large cavity 24 , (4) their structures, properties and functions can be tailored easily by protein engineering and recombinant DNA techniques 25 , and (5) multivalency for chemical functionalizations or genetic modifications 26,27 .…”

Amino Acid Side Chains Buried along Intersubunit Interfaces in a Viral Capsid Preserve Low Mechanical Stiffness Associated with Virus Infectivity

“…Virus-based NPs are being tested, for example, as nanocontainers for targeted drug delivery; contrast agents for medical imaging; nanobiosensors; light harvesting devices; or templates to obtain metallic NPs for producing catalysts, batteries, electronic circuits and memory devices. [36][37][38][39][40][41][42][43] Unfortunately, natural virus particles may not withstand the harsh conditions and mechanical forces they could meet during production 44 and/or use. In addition, the lower stiffness of many virus particles compared to other NPs may make them inadequate for applications where a precise distance between active components must be preserved (e.g., between donor and acceptor in a light-harvesting NP 42 ).…”