Sequencing of Polyclonal Antibodies by Integrating Intact Mass, Middle-Down, and De Novo Bottom-Up Mass Spectrometry.

ABSTRACT: Polyclonal antibodies (pAbs) represent nature's approach to robust immunity, targeting multiple sites on pathogens, but their complex mixtures have remained largely unsequenceable, limiting their therapeutic potential. While monoclonal antibodies (mAbs) dominate therapeutics because of their reproducibility, pAbs offer superior resilience against viral mutations and broader target recognition. Current pAb sequencing attempts have shown limitations, requiring germline databases or B-cell sequencing. Due to the highly variable nature of antibodies, as well as the possibility of unavailable B cells, there is a need for a purely mass spectrometry- and de novo sequencing-based solution. Here, we present PolySeq.AI, an automated de novo workflow that combines bottom-up, middle-down, and intact m

SUBMITTER: Xin L 

PROVIDER: S-EPMC12639833 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature