From stars to stripes: RNA‐directed shaping of plant viral protein templates—structural synthetic virology for smart biohybrid nanostructures

Abstract

The self‐assembly of viral building blocks bears exciting prospects for fabricating new types of bionanoparticles with multivalent protein shells. These enable a spatially controlled immobilization of functionalities at highest surface densities—an increasing demand worldwide for applications from vaccination to tissue engineering, biocatalysis, and sensing. Certain plant viruses hold particular promise because they are sustainably available, biodegradable, nonpathogenic for mammals, and amenable to in vitro self‐organization of virus‐like particles. This offers great opportunities for their redesign into novel “green” carrier systems by spatial and structural synthetic biology approaches, as worked out here for the robust nanotubular tobacco mosaic virus (TMV) as prime example. Natural TMV of 300 x 18 nm is built from more than 2,100 identical coat proteins (CPs) helically arranged around a 6,395 nucleotides ssRNA. In vitro, TMV‐like particles (TLPs) may self‐assemble also from modified CPs and RNAs if the latter contain an Origin of Assembly structure, which initiates a bidirectional encapsidation. By way of tailored RNA, the process can be reprogrammed to yield uncommon shapes such as branched nanoobjects. The nonsymmetric mechanism also proceeds on 3'‐terminally immobilized RNA and can integrate distinct CP types in blends or serially. Other emerging plant virus‐deduced systems include the usually isometric cowpea chlorotic mottle virus (CCMV) with further strikingly altered structures up to “cherrybombs” with protruding nucleic acids. Cartoon strips and pictorial descriptions of major RNA‐based strategies induct the reader into a rare field of nanoconstruction that can give rise to utile soft‐matter architectures for complex tasks. This article is categorized under: Biology‐Inspired Nanomaterials > Protein and Virus‐Based Structures Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Biology‐Inspired Nanomaterials > Nucleic Acid‐Based Structures

Field-Effect Sensors for Virus Detection: From Ebola to SARS-CoV-2 and Plant Viral Enhancers

“…Here, EIS structures with adsorbed TMV particles were used for designing a penicillin biosensor, where the TMV particles served as nanocarriers for enzymes installed at high surface densities on the viral coat protein (CP) subunits. TMV has a nanotube-like structure with a single RNA molecule and 2,130 CPs helically assembled into full-length particles of 300 nm, outer diameter of 18 nm and a longitudinal internal channel of 4 nm diameter (Klug, 1999;Scholthof et al, 1999;Culver, 2002;Lomonossoff and Wege, 2018;Wege and Koch, 2020). TMV is harmless for mammals (Nikitin et al, 2016) and lacks a membrane envelope; it and related tobamoviruses infect numerous plant species in several families through mechanical transmission fast and efficiently (Zaitlin, 2000;Adams et al, 2017).…”

“…Since more than two decades, several plant viruses attract increasing attention also from a different point of view: Their precise and robust nanostructures with repetitively organized, multivalent protein surfaces lend these viruses and derivatives thereof to uses in medical and technical environments, as carrier particles for the delivery and/or display of functional units enclosed and/or exposed at high densities (Bittner et al, 2013;Lin and Ratna, 2014;Culver et al, 2015;Khudyakov and Pumpens, 2016;Koch et al, 2016;Wen and Steinmetz, 2016;Dragnea, 2017;Steele et al, 2017;Lomonossoff and Wege, 2018;Wege and Lomonossoff, 2018;Balke and Zeltins, 2019;Chen et al, 2019;Eiben et al, 2019;Roeder et al, 2019;Chung et al, 2020;Wege and Koch, 2020;Wen et al, 2020). The respective plant viruses and VLPs are richly and sustainably available by farming (Marsian and Lomonossoff, 2016;Gowtham and Sathishkumar, 2019;Rybicki, 2020), and despite a remarkable durability biodegradable after use.…”

“…The respective plant viruses and VLPs are richly and sustainably available by farming (Marsian and Lomonossoff, 2016;Gowtham and Sathishkumar, 2019;Rybicki, 2020), and despite a remarkable durability biodegradable after use. Certain plant viral CPs are amenable to modifications facilitating the selective coupling of functional molecules, and to in vivo or in vitro assembly into VLPs even in the absence of viral nucleic acids (Wege and Koch, 2020). This allows the fabrication of artificial, bioinstructive carrier particles of adapted shapes and surface chemistries.…”

“…The largest and most advanced area of medical uses are plant VLP-based self-adjuvanting vaccines (Chackerian, 2007;Crisci et al, 2012;Matić and Noris, 2015;Hefferon, 2018;Balke and Zeltins, 2020;Rybicki, 2020;Santoni et al, 2020) with candidates against COVID-19 in the developmental pipelines of at least two companies (Rosales-Mendoza, 2020), as specified also in this research topic. Similarly, plant viral particles are being evaluated on various technological platforms that gain enhanced or even novel functionality through an integration of multivalent, selectively addressable bionanostructures (Fan et al, 2013;Culver et al, 2015;Koch et al, 2016;Dragnea, 2017;Narayanan and Han, 2017;Chu et al, 2018a;Chen et al, 2019;Wege and Koch, 2020). Uses as templates for inorganic and synthetic compounds have led to biohybrid materials of convincing properties (Douglas and Young, 1998;Bittner et al, 2013;Vilona et al, 2015;Tiu et al, 2016;Wen and Steinmetz, 2016;Lee et al, 2017;Zhang et al, 2018;Eiben et al, 2019), such as high-capacity battery electrodes or spatially ordered dye ensembles for light-harvesting.…”

“…In this review, recent advances and key developments in the field of label-free detection of viruses (including plant viruses) with various types of BioFEDs are presented. Plant viruses are additionally introduced as promising bionanotools and building blocks of smart materials (e.g., Mao et al, 2009;Culver et al, 2015;Khudyakov and Pumpens, 2016;Koch et al, 2016;Wen and Steinmetz, 2016;Dragnea, 2017;Steele et al, 2017;Chu et al, 2018a;Lomonossoff, 2018;Lomonossoff and Wege, 2018;Wege and Lomonossoff, 2018;Chen et al, 2019;Eiben et al, 2019;Wege and Koch, 2020;Wen et al, 2020) that may bring about novel options for biosensor technology if applied as model particles, signal-amplifying colloids or, most importantly, multivalent adapter templates for the high surface-density presentation of detector components.…”