Engineering a novel light-chain single-domain antibody to enable IgG-format bispecific antibody design.

ABSTRACT:

Background

As one of the most promising classes of next-generation antibody therapeutics, bispecific antibodies (bsAbs) have gained increasing attention owing to their unique dual-targeting mechanisms. However, current bsAb formats often face challenges such as low expression levels, poor homogeneity, and unstable therapeutic efficacy due to their complex structures. Therefore, it is urgent to overcome the current technical limitations and develop novel formats of bsAbs with more stable structures and improved expression efficiency.

Methods

Through rational design and phage display-based screening, we engineered a novel light-chain single-domain antibody (VHHL). Using modular assembly and replacement strategies, the VHHL was reconstituted into conventional immunoglobulin G (

SUBMITTER: Wang M 

PROVIDER: S-EPMC12598741 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature