Design and characterization of Structure-Based Variants of Staphylokinase for the Development of Deimmunized Biotherapeutics

Sarkar, Monalisa (2023) Design and characterization of Structure-Based Variants of Staphylokinase for the Development of Deimmunized Biotherapeutics. Masters thesis, Indian Institute of Science Education and Research Kolkata.

Text (MS dissertation of Monalisa Sarkar (18MS020)) Thesis_18MS020.pdf - Submitted Version Restricted to Repository staff only Download (18MB)

Abstract

Owing to their versatility, proteins have garnered considerable interest, particularly in bio therapeutics. The majority of native proteins cannot be employed as effective drugs; therefore, novel generations of therapeutic proteins that have been designed to increase process features or improve product properties are required. The immunogenicity of proteins in biotherapeutics is a challenge. Numerous nonhuman proteins with potential biotherapeutics have been rejected owing to immunogenicity concerns. With the long term goal of developing a generalized deimmunization approach at protein biotherapeutics, we drew inspiration from the "antibody humanization" concept. We are developing a pipeline that will allow the deimmunization of any protein of our choice. For my project Staphylokinase was taken as a model. Being a potential clot buster in protein biotherapeutics, the primary issue arises with its immunogenicity. With Stapylokinase and its engineered variants with conformational change based on secondary structure, 20 of these variants were suppressed, 10 of them were purified and 5 were biochemically characterised.

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