Protein re-surfacing of E. coli L-Asparaginase to evade pre-existing anti-drug antibodies and hypersensitivity responses.

ABSTRACT: The optimal use of many biotherapeutics is restricted by Anti-drug antibodies (ADAs) and hypersensitivity responses which can affect potency and ability to administer a treatment. Here we demonstrate that Re-surfacing can be utilized as a generalizable approach to engineer proteins with extensive surface residue modifications in order to avoid binding by pre-existing ADAs. This technique was applied to E. coli Asparaginase (ASN) to produce functional mutants with up to 58 substitutions resulting in direct modification of 35% of surface residues. Re-surfaced ASNs exhibited significantly reduced binding to murine, rabbit and human polyclonal ADAs, with a negative correlation observed between binding and mutational distance from the native protein. Reductions in ADA binding correlated

SUBMITTER: Bootwala A 

PROVIDER: S-EPMC9767956 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature