attenuated diphtheria toxin A subunit

Attenuated diphtheria toxin A subunit (DTA) is a cytotoxic payload utilized in experimental nucleic acid therapeutics, specifically those targeting cancers characterized by SF3B1 mutations. Developed by researchers at Johns Hopkins University, this therapeutic approach leverages a splicing-dependent expression system. By utilizing a cryptic exon inclusion event (such as that found in the UBA1 gene) which occurs selectively in the presence of mutant SF3B1, the DTA cargo is expressed exclusively within malignant cells. Once translated, the DTA protein catalyzes the ADP-ribosylation of eukaryotic translation elongation factor 2 (EEF2), effectively halting protein synthesis and inducing apoptosis. The use of an attenuated version of the toxin is intended to minimize potential off-target toxicity that might arise from low-level 'leaky' expression in healthy cells. This therapeutic is typically delivered via adeno-associated viral (AAV) vectors or plasmids and is being investigated for indications such as acute myeloid leukemia (AML), uveal melanoma, and pancreatic carcinoma.

Other names

attenuated DTAdiphtheria toxin A subunit