RNase-H-mediated silencing in the CNS proves predictably nontrivial

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease primarily affecting motor neurons. Recently, Miller et al. presented phase 3 data for the RNase-H-recruiting antisense oligonucleotide (ASO) targeting superoxide dismutase 1 (SOD1) in ALS, which represents a step forward in the deployment of ASO therapeutics against CNS targets.