2023-11-24 20:15:49
Scientists have managed to use plants as biofactories to produce nanoparticles that serve as drug carriers.
Specifically, they have created nanoparticles with small single-chain monoclonal antibodies (nanobodies) that act against the protein that surrounds the SARS-CoV-2 coronavirus. These nanoparticles could be used as a reagent in diagnostic tests and, after evaluation, as a drug to neutralize virus infection.
The achievement is the work of a team from the Institute of Molecular and Cellular Biology of Plants (IBMCP), a joint center of the Higher Council for Scientific Research (CSIC) and the UPV (Universitat Politècnica de València), in collaboration with the Institute of Integrative Biology of Systems (I2SySBio), from the CSIC and the UV (Universitat de València).
The research group led by José Antonio Darós at the IBMCP used plants of the species Nicotiana benthamiana 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 launch other mechanisms that destroy elements potentially dangerous to the body (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 humanity. Now the process is modified, turning the 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, research professor at the CSIC in the IBMCP. To do this, they use the ability of viruses to infect plants quickly and systemically, inserting the gene that codes for the antibody they want to produce into the virus genome.
“Instead of producing these nanobodies as individual molecules, in this project we develop the production of nanoparticles, molecular structures whose scale is nanometric, which serve as a support for the presentation of said 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 repetitions of the antibody in question,” he describes. This increases its capacity for action, since “multivalent nanobodies show greater avidity towards their target and, therefore, are more powerful in neutralizing it.”
IBMCP researcher Fernando Merwaiss. (Photo: UPV)
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 subsequent step, their ability to also be used as therapeutic agents capable of inhibiting viral spread could be evaluated,” comments Fernando Merwaiss, postdoctoral researcher at the IBMCP and co-principal investigator of the study.
Regarding the advantages of using plants as biofactories to generate compounds of pharmacological interest, in addition to the low production cost (plants only need sunlight, water, carbon dioxide and some inorganic nutrients to grow), “it has other advantages such as unlikelihood of contamination with human pathogens, the ease of scaling production and the ability to perform post-translational modifications similar to those of mammalian cells,” Merwaiss highlights. Furthermore, 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.
The study is titled “Plant virus-derived nanoparticles decorated with genetically encoded SARS-CoV-2 nanobodies display enhanced neutralizing activity.” And it has been published in the academic journal Plant Biotechnology Journal. (Source: Isidoro García Cano / CSIC)
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