Abstract
Bckground: One of the major challenges of biopharmaceuticals having short plasma half-life is that daily high dose injections are needed which can lead to economic burden, patient inconvenience and undesirable side effects. Increasing the hydrodynamic volume beyond the pore size of the glomerular basal membrane is a viable approach to increase the size of small biopharmaceuticals with short half-life in blood circulation.
Objectives: PASylation technology is based on the genetic fusion of biopharmaceuticals with a hydrophilic random coil sequence of proline (Pro), alanine (Ala), and serine (Ser) amino acids.
Method: In this review, we focus on PASylation technology as a novel method to enhance the pharmacokinetic (PK) properties of biopharmaceuticals.
Results: PASylated biopharmaceuticals are suitable for the production in Escherichia coli (E.coli) as well as eukaryotic expression systems like yeast, HEK or CHO cells and comprise a homogeneous PAS sequence with exact length.We explain the general concept of PASylation, its development; advantages compared to other PK modifying technologies and describe furthermore the pharmacodynamic (PD) and PK properties of several PAS-fusion proteins in preclinical studies.
Conclusion: The biodegradable PAS sequence was already used for prolonging plasma half-life of clinical important agents such as antibody fragments, cytokines, enzymes and receptor-binding peptides.
Keywords: PASylation, tumor targeting, ESETEC technology, biodistribution, radiopharmaceutical, biopharmaceutical.
Graphical Abstract
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