Currently, acute lymphoblastic leukemia (ALL) is the most frequent type of cancer seen in children. One of the main types of treatments available recently is the administration of L-asparaginase (L-ASNase). This enzyme presents itself in different dosage forms in the market, distinguishing within each other either by its source (Escherichia coli ou Erwinia chrysanthemi) or by chemical modifications. However, many of those biopharmaceuticals have some disadvantages, since they may induce some immunogenic reactions and be rapidly cleared from our organism by different elimination processes. Based on this, the focal point of our project is to express L-ASNase enzyme with a glycosylated structure, aiming a less responsive immune reaction and increase in its therapeutical effect. For this, we intend to clone L-ASNase from Escherichia coli in eukaryotic organisms, more precisely yeasts from a genetic modified strain of Pichia pastoris. The goal of this project is to assess if the strain is capable of producing humanized glycosylated proteins as well as secreting it outer of the cell with high efficiency. Therefore, the glycosylation would facilitate the masking of our enzyme, a strategy that could then allow a more efficient therapeutical effect for our biopharmaceutical protein in order to treat ALL.
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