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Using plants to create nanoparticles with antibodies against SARS-CoV-2

  • November 22nd, 2023
 

Scientist from the Institute for Plant Molecular and Cellular Biology (CSIC-UPV) have obtained nanoparticles coated in antibodies against the coronavirus from plant “bio-factories”. This method for producing antibodies, developed along with the Institute for Integrative Systems Biology (CSIC-UV), is both economical and avoids contamination with human pathogens.

The ability to use plants as “bio-factories” to produce nanoparticles as drug vehicles. This is what was discovered by a research team at the Institute for Plant Molecular and Cellular Biology (IBMCP), a mixed centre of the Spanish Research Council (CSIC) and the Universitat Politècnica de València (UPV), in collaboration with the Institute for Integrative Systems Biology (I2SySBio), of the CSIC and the Universitat de València. Specifically, they created nanoparticles with small single-chain monoclonal antibodies (nanobodies) that act against the protein enveloping the coronavirus SARS-CoV-2. These nanoparticles can be employed as a reagent in diagnostic tests and, after further evaluation, as a drug to neutralise the viral infection. The results are published in the Plant Biotechnology Journal.

The research group led by José Antonio Darós at the IMBCP used plants from the Nicotiana benthamiana species to produce nanoparticles covered in small single-chain monoclonal antibodies called nanobodies. Antibodies are essential molecules of the immune system that are capable of binding to any foreign structure in order to initiate other mechanisms that destroy elements potentially dangerous to the organism (viruses, bacteria, tumours, etc.). Specifically, the nanobodies obtained in this project act against the S protein of SARS-CoV-2, the so-called “key” that allows the coronavirus to infect cells.

Obtaining pharmaceutical drugs from plants dates back to the dawn of humanity. Today, the process is being modified, turning plants into factories to produce compounds of interest. “In the same way that naturally occurring compounds can be extracted from plants, we induce the production of the molecule that we want, in this case nanoparticles covered in nanobodies,” explains José Antonio Darós, professor of research from CSIC at the IBMCP. To do so, they use the viruses’ ability to infect plants rapidly and systemically by inserting into the virus genome the gene encoding the antibody they want to produce.

“Instead of producing these nanobodies as individual molecules, in this project we are developing the production of nanoparticles, molecular structures that are nanometre-sceale, which act as carriers for the delivery of these antibodies,” says Darós. The nanoparticle that they use is the viral particle itself, whose structural protein is fused to an antibody. “Thus by self-assembling these structural proteins, we obtain multivalent macromolecules, which have hundreds of copies of the antibody in question,” he continues. This increases its capacity for action, given that “the multivalent nanobodies show greater avidity towards their target and are therefore more potent at neutralising it.”

Advantages to using plants as bio-factories

This system for the production of multivalent nanoparticles in plant bio-factories can be used to produce any nanobody of interest, the researchers say. “In particular, the nanoparticles developed in this project can be used as a reagent in diagnostic tests of coronavirus, such as widely marketed test strips. And in a later step, their ability to be used as therapeutic agents capable of inhibiting viral spread could be evaluated,” says Fernando Merwaiss, postdoctoral researcher at the IBMCP and co-lead author of the study.

Regarding the advantages of using plants as bio-factories to generate compounds of pharmacological interest, in addition to the low cost of production (the plants only need sunlight, water, carbon dioxide and some inorganic nutrients to grow), “it has other advantages such as the low probability of contamination with human pathogens, the ease of scaling up production and the ability to perform post-translational modifications similar to those in mammalian cells,” adds Merwaiss. Furthermore, the method developed by the IBMCP and I2SysBio teams offers the possibility of producing hundreds of nanobodies clustered on a single multivalen macromolecule, which significantly increases their capacity for action.

References:

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

Source: CSIC