In the present study, we applied the PASylation® technology in order to overcome both of these obstacles of the currently available Tα1 drug and to create a long-lasting N-terminally acetylated therapeutic peptide, also offering cheap and efficient biotechnological production in E. coli. To this end, we combined fusion with a 600-residue polypeptide comprising the small natural L-amino acids Pro, Ala, and Ser [31] with in situ N-acetylation by overexpressing the host cell N-acetyltransferase RimJ [32]. The genetically encoded uncharged “PAS” sequence is highly soluble and structurally disordered, with an expanded hydrodynamic volume, thus showing a biophysical behavior very similar to the chemical polymer polyethylene glycol (PEG), which has been utilized for plasma half-life extension of a series of other therapeutic peptides and proteins [33,34,35].