Fusion Protein Therapeutics Conference – May 1-2
PASylation: The Biological Alternative to PEGylation for Plasma Half-Life Extension and Beyond
Arne Skerra, Ph.D., Professor, Technische Universität Munich; and Chairman & Founder, XL-protein GmbH
Fusion of proteins or peptides with conformationally disordered polypeptides comprising the L-amino acids Pro, Ala, and/or Ser (PAS) is a beneficial way to enlarge the hydrodynamic volume and retard kidney clearance, a common drawback during biological drug development. PAS sequences are strongly hydrophilic, uncharged biological polymers with biophysical properties surprisingly similar to PEG while, in contrast, allowing traceless metabolization. Case studies on the route to clinical development will be presented.
Q. What are the benefits of PASylation?
PASylation is a biological alternative to PEGylation based on random coil polypeptides with defined length and sequence made of the small natural amino acids Pro, Ala and/or Ser. PAS polypeptides can be cheaply produced by recombinant gene expression in various host organisms; they are biodegradable but stable in blood. Additional benefits include strict monodispersity, high solubility and lack of charges.
Q. How do you employ this technology?
PAS polypeptides can be conjugated to biopharmaceuticals both via genetic fusion and via chemical conjugation. PASylation can serve to strongly extend the plasma half-life of biologics (by way of retarded kidney filtration) in a tunable manner and, thus, boost pharmaceutical activity. PASylation is also useful to shield protein drugs from immune recognition. Finally, PAS polypeptides can be employed as flexible linkers to create bispecific/bifunctional fusion proteins by combining various proteins or peptides.
Q. What is the history of PASylation and its discovery?
PASylation technology was discovered at the Technical University of Munich, Germany, in the course of basic research aimed at designing natively disordered though uncharged recombinant polypeptides that mimic the biophysical properties of poly-ethylene glycol (PEG) with its expanded hydrodynamic volume. After scientific proof of concept the biotech company XL-protein GmbH was founded in Germany in order to develop PASylated therapeutics and commercially exploit the technology.
Q. What are you most looking forward to at the upcoming PEGS Summit?
I am looking forward to meeting renowned experts during this internationally leading conference in order to exchange new ideas and to discuss opportunities for collaboration. I will present our latest applications of PASylation technology for biological drug development, projects on the route towards clinical study as well as fundamental insights into the polymer biophysics of PAS sequences.