WITHDRAWN: (CA)_noligonucleotides correct RNA mis-splicing in TDP-43 pathology

Abstract

The occurrence of extensive cryptic splicing following the depletion of nuclear TDP-43 results in impaired neuronal function and degeneration. Here, we designed oligonucleotides containing CA-repeat sequences which mimic TDP-43 pre-mRNA binding. Treating TDP-43-depleted neurons with (CA)noligonucleotide can broadly repress cryptic splicing events, subsequently reverse protein loss, and restore neuronal activity. Importantly, (CA)nASO did not induce major gene expression changes or cytotoxicity in healthy neurons. Our results demonstrate that (CA)noligonucleotides are potential therapeutic agents to address global mis-splicing in TDP-43 proteinopathies.