A new class of recombinant human albumin with multiple surface thiols exhibit stable conjugation, and enhanced FcRn binding and blood circulation.
Schelde KK1, Nicholls K2, Dagnæs-Hansen F3, Bunting K2, Rawsthorne H2, Andersen B4, Finnis CJA2, Williamson M2, Cameron J2, Howard KA3.
- 1 iNANO, Aarhus University, Denmark.
- 2 Albumedix Ltd, United Kingdom.
- 3 Aarhus University, Denmark.
- 4 Novozymes A/S.
"Human serum albumin is an endogenous ligand transport protein whose long circulatory half-life is facilitated by engagement with the humancellular recycling neonatal Fc receptor (hFcRn). The single free thiol located at Cys-34 in domain I of albumin has been exploited for monoconjugation of drugs. In this work, we increased the drug-to-albumin ratio potential by engineering recombinant human albumin (rHSA) variants with varying hFcRn affinity to contain three free, conjugation-competent cysteines."