Human serum albumin binders: A piggyback ride for long-acting therapeutics

Human serum albumin (HSA) is the most abundant protein in the blood and has desirable properties as a drug carrier. One of the most promising ways to exploit HSA as a carrier is to append an albumin-binding moiety (ABM) to a drug for in situ HSA binding upon administration. Nature- and library-derived ABMs vary in size, affinity, and epitope, differentially improving the pharmacokinetics of an appended drug. In this review, we evaluate the current state of knowledge regarding various aspects of ABMs and the unique advantages of ABM-mediated drug delivery. Furthermore, we discuss how ABMs can be specifically modulated to maximize potential benefits in clinical development.