Biopharmazeutika mit verlängerter Wirkdauer durch PASylation

Translated title of the contribution: Biopharmaceuticals with prolonged action through PASylation

Uli Binder, Arne Skerra

Research output: Contribution to journalArticlepeer-review

Abstract

Rapid clearance from blood circulation by renal filtration is a typical drawback of most therapeutic proteins and peptides (except for full size antibodies), in particular established biologics such as hormones, growth factors, cytokines and enzymes, but also immunoglobulin fragments (Fab, scFv or single domain/nanobody). Chemical conjugation with poly-ethylene glycol (PEG), which expands the effective molecular size beyond the threshold of kidney filtration, is a well known strategy to prolong the short plasma half-life of biopharmaceuticals to a clinically useful range. However, coupling with the synthetic polymer PEG requires expensive material and additional downstream procedures and, furthermore, PEG can accumulate in organs due to its lack of biodegradability. An alternative is the use of conformationally disordered polypeptide chains with large hydrodynamic volume comprising the small amino acid residues proline, alanine, and/or serine (PAS). PAS sequences are hydrophilic, uncharged biological polymers with biophysical properties surprisingly similar to PEG. In contrast, PAS polypeptides offer fusion to a biological drug on the genetic level, permitting facile production of fully active proteins in E. coli or in eukaryotic cell culture and obviating in vitro coupling or modification steps. Also, PAS polymers are biodegradable, thus avoiding tissue accumulation, while showing stability in plasma and lacking toxicity or immunogenicity in animals. Hence, PASylation® provides a modular technology to design superior novel biologics or so-called biobetters.

Translated title of the contributionBiopharmaceuticals with prolonged action through PASylation
Original languageGerman
Pages (from-to)278-282
Number of pages5
JournalPharmazeutische Industrie
Volume77
Issue number2
StatePublished - 2015
Externally publishedYes

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