Research personnel from the Institute of Integrative Systems Biology (I2SysBio), of the scientific area of the University of Valencia Science Park (PCUV), are participating in a study that manages to obtain nanoparticles coated with antibodies against the coronavirus from plant 'biofactories'. This method to produce antibodies, developed together with the Institute of Molecular and Cellular Biology of Plants (CSIC-UPV), is economical and avoids contamination with human pathogens
The project, in which the Institute of Integrative Systems Biology (I2SysBio, CSIC-UV), located at the University of Valencia Science Park (PCUV), is participating, manages to create nanoparticles with small single-chain monoclonal antibodies (nanobodies) that act against the protein that envelops the SARS-CoV-2 coronavirus. These nanoparticles could be used as a reagent in diagnostic tests and, after evaluation, as a drug to neutralize the virus infection. The results are published in the Plant Biotechnology Journal. This achievement was made by a team from I2SySBio in collaboration with the Institute of Molecular and Cellular Biology of Plants (IBMCP), a joint center of the Spanish National Research Council (CSIC) and the Polytechnic University of Valencia (UPV).
The research group led by José Antonio Darós at the IBMCP used plants of the Nicotiana benthamiana species to produce nanoparticles coated with small single-chain monoclonal antibodies, also called 'nanobodies'. Antibodies are essential molecules of the immune system, capable of binding to any foreign structure to trigger other mechanisms that destroy potentially dangerous elements for the organism (viruses, bacteria, tumor cells...). Specifically, the nanobodies obtained in this work act against the S protein of SARS-CoV-2, the 'key' that allows the coronavirus to infect cells.
Obtaining drugs from plants dates back to the dawn of mankind. Now the process is being modified, turning plants into factories to produce compounds of interest. "In the same way that a compound produced naturally by a plant can be extracted, we induce the production of the molecule we want, in this case nanoparticles coated with nanobodies," explains José Antonio Darós, CSIC research professor at the IBMCP. To do this, they use the ability of viruses to infect plants quickly and systemically, inserting the gene encoding the antibody they want to produce into the virus genome.
Along with the possibility of using plants as biofactories to generate compounds of pharmacological interest, in addition to the low cost of production, it has advantages such as the improbability of contamination with human pathogens, the ease of scaling up production and the ability to perform post-translational modifications similar to those of mammalian cells
"Instead of producing these nanobodies as individual molecules, in this project we developed the production of nanoparticles, molecular structures on a nanometer scale, which serve as a support for the presentation of these antibodies," reveals Darós. The nanoparticle they use is the viral particle itself, whose structural protein is fused to an antibody. "In this way, when these structural proteins self-assemble, we obtain multivalent macromolecules, which have hundreds of repeats of the antibody in question," he describes. This increases their capacity for action, since "the multivalent antibodies show greater avidity towards their target and are therefore more potent in neutralizing it."
Advantages of using plants as biofactories
This system for producing multivalent nanoparticles in plant biofactories could be used to produce any nanobody of interest, the researchers say. "In particular, the nanoparticles developed in this work could be used as a reagent in coronavirus diagnostic tests, such as the widely marketed test strips. In a further step, their ability to be used also as therapeutic agents capable of inhibiting viral propagation could be evaluated," says Fernando Merwaiss, postdoctoral researcher at the IBMCP and co-lead author of the study.
Along with the possibility of using plants as biofactories to generate compounds of pharmacological interest, in addition to the low cost of production (plants only need sunlight, water, carbon dioxide and some inorganic nutrients to grow), "it has other advantages such as the unlikelihood of contamination with human pathogens, the ease of scaling up production and the ability to perform post-translational modifications similar to those of mammalian cells," Merwaiss remarks. In addition, the method developed by the IBMCP and I2SysBio team adds the possibility of producing hundreds of nanobodies grouped in the same multivalent macromolecule, which significantly increases their capacity for action.
Merwaiss, F., Lozano-Sanchez, E., Zulaica, J., Rusu, L., Vazquez-Vilar, M., Orzáez, D., Rodrigo, G., Geller, R. and Daròs, J.-A. (2023), Plant virus-derived nanoparticles decorated with genetically encoded SARS-CoV-2 nanobodies display enhanced neutralizing activity. Plant Biotechnol. J. DOI: https://doi.org/10.1111/pbi.14230