RT Journal Article
T1 Targeted Cancer Cell Killing by Highly Selective miRNA-Triggered Activation of a Prokaryotic Toxin-Antitoxin System.
A1 Turnbull, Alice
A1 Bermejo-Rodríguez, Camino
A1 Preston, Mark A
A1 Garrido-Barros, María
A1 Pimentel, Belén
A1 de la Cueva-Méndez, Guillermo
K1 Kid-Kis
K1 cancer cell killing
K1 gene therapy
K1 miR373
K1 onco-miRNA
K1 toxin−antitoxin
AB Although not evolved to function in eukaryotes, prokaryotic toxin Kid induces apoptosis in human cells, and this is avoided by coexpression of its neutralizing antitoxin, Kis. Inspired by the way Kid becomes active in bacterial cells we had previously engineered a synthetic toxin-antitoxin system bearing a Kis protein variant that is selectively degraded in cells expressing viral oncoprotein E6, thus achieving highly selective killing of cancer cells transformed by human papillomavirus. Here we aimed to broaden the type of oncogenic insults, and therefore of cancer cells, that can be targeted using this approach. We show that appropriate linkage of the kis gene to a single, fully complementary, target site for an oncogenic human microRNA enables the construction of a synthetic toxin-antitoxin pair that selectively kills cancer cells overexpressing that particular microRNA. Importantly, the resulting system spares nontargeted cells from collateral damage, even when they overexpress highly homologous, though nontargeted, microRNAs.
YR 2019
FD 2019-08-01
LK http://hdl.handle.net/10668/14311
UL http://hdl.handle.net/10668/14311
LA en
DS RISalud
RD Apr 11, 2025