|Sub Research Field:
Identification and development of monoclonal antibodies against a conserved region of SARS-CoV-2 and employment of antibody engineering approaches to transform them into potent neutralizers.
Identification of broadly neutralizing mAbs targeting the MPER region of SARS-CoV-2. Monoclonal antibodies will be isolated using single B cell cloning techniques and expressed in mamalian 293F cells for their purification and biophysical characterization (binding kinetics and stability measurements). Neutralization potency and breadth of the isolated antibodies will be measured using molecularly cloned S-pseudotyped viruses.
Potentiation of the neutralizing capacity of anti-MPER mAbs through protein engineering. The structure of the five mAbs with the best biophysical and functional properties will be solved in complex with its peptide epitope by X-ray crystallography. These molecular details will be used to guide the design of antibodies with improved biological functions.
Development of a nucleic acid delivery platform based on LNP that encode a monoclonal antibody. Plasmid DNA and nucleoside-modified mRNA encoding for the lead engineered antibody will be designed and formulated in LNPs. In order to optimize the LNP-based non-viral vectors, formulation composition, inclusion of different ligands (peptides, polysaccharides, etc) and technological factors will be tested. Transfection efficiency and cell viability studies of the optimized DNA and mRNA vectors will be tested in vitro in different cell models.
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