Engineering Agonistic Bispecifics to Investigate the Influence of Distance on Surface-Mediated Complement Activation.

ABSTRACT: The development of agonists capable of activating the human complement system by binding to the C1 complex presents a novel approach for targeted cell killing. Bispecific nanobodies and Abs can successfully use C1 for this purpose; however, efficacy varies significantly between epitopes, Ab type, and bispecific design. To address this variability, we investigated monomeric agonists of C1 in the form of bispecific nanobodies, which lack Fc domains that lead to oligomerization in Abs. These therefore offer an ideal opportunity to explore the geometric parameters crucial for C1 activation. In this study, we explored the impact of linker length as a metric for Ag and epitope location. DNA nanotechnology and protein engineering allowed us to design linkers with controlled lengths and flexibilit

SUBMITTER: Hamers SMWR 

PROVIDER: S-EPMC11215631 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature