PASylation®: A versatile technology to extend drug delivery

PASylation® technology comprises the conjugation – via genetic fusion or chemical coupling – of pharmacologically active compounds, such as proteins, peptides and low molecular weight drugs, with natively disordered biosynthetic polymers made of the small L-amino acids Pro, Ala and/or Ser. Such proline/alanine-rich sequences (PAS) are highly soluble in physiological solution and stably adopt random coil conformation, which results in an expanded hydrodynamic volume. Consequently, PAS-drug conjugates show retarded kidney filtration and drastically prolonged pharmacokinetics (PK) in vivo. The intrinsically uncharged PAS polypeptides do not interfere with the pharmacological activity of the drug component and show high stability in plasma as well as no immunogenicity, while undergoing quick degradation and metabolization after cellular uptake. PASylation has been successfully applied to a wide range of pharmacologically active proteins and peptides, including hormones, cytokines, antibody fragments and enzymes, as well as nanocarriers. This review discusses the fundamental concepts of PASylation technology and recent advances in preclinical applications.