antisense oligonucleotides targeting stathmin-2

Antisense oligonucleotides (ASOs) targeting stathmin-2 (STMN2) are a class of RNA-targeted therapeutics designed to restore the expression of stathmin-2, a microtubule-binding protein essential for axonal growth, maintenance, and repair. In amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), the nuclear loss of the RNA-binding protein TDP-43 leads to the aberrant inclusion of a cryptic exon (exon 2a) in STMN2 pre-mRNA, resulting in premature polyadenylation, transcript degradation, and stathmin-2 protein depletion. Splice-switching ASOs bind to the cryptic splice region of STMN2 pre-mRNA, preventing aberrant splicing and restoring full-length stathmin-2 protein levels to promote axonal regeneration. Clinical-stage candidates in this class, such as QurAlis' QRL-201, are administered intrathecally and have demonstrated target engagement and biomarker reduction in clinical trials.

Other names

STMN2 antisense oligonucleotidesSTMN-2 antisense oligonucleotidesSTMN 2 antisense oligonucleotidesstathmin-2 antisense oligonucleotidesstathmin2 antisense oligonucleotidesstathmin 2 antisense oligonucleotides