Genetic algorithm for deimmunization of Escherichia coli L-asparaginase

Abstract

Introduction: L-asparaginase is a heterologous enzyme expressed in Escherichia coli and used in leukemya therapy that triggers an immune response due to the presence of linear T-cell epitopes within the protein sequence. This results in the sustained production of antibodies that causes hypersensitivity problems and in the neutralization of the therapeutic effect. To diminish the potential immunogenicity, the protein can be subject to a process of epitope deletion via genetic manipulation of key MHC-high-binding residues. As an exhaustive evaluation of the mutants is prohibitive for experimental scientist because the number of variants is too big, in silico tools can be used to diminish the search space.