A Biparatopic Intrabody Renders Vero Cells Impervious to Ricin Intoxication

Overview

Journal bioRxiv

Date 2024 Jul 15

PMID 39005371

Authors

Timothy F Czajka

David J Vance

Renji Song

Nicholas J Mantis

Affiliations

Soon will be listed here.

Abstract

Expression of camelid-derived, single-domain antibodies (VHs) within the cytoplasm of mammalian cells as "intrabodies" has opened-up novel avenues for medical countermeasures against fast-acting biothreat agents. In this report, we describe a heterodimeric intrabody that renders Vero cells virtually impervious to ricin toxin (RT), a potent Category B ribosome-inactivating protein (RIP). The intrabody consists of two structurally defined VHs that target distinct epitopes on RT's enzymatic subunit (RTA): V9E1 targets RTA's P-stalk recruitment site, and V2A11 targets RTA's active site. Resistance to RT conferred by the biparatopic VH construct far exceeded that of either of the VHs alone and effectively inhibited all measurable RT-induced cytotoxicty . We propose that targeted delivery of bispecific intrabodies to lung tissues may represent a novel means to shield the airways from the effects of inhalational RT exposure.

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