The recent discontinuation of four Huntington’s disease ASO clinical trials, which had targeted huntingtin transcripts, as well as mixed results from amyotrophic lateral sclerosis (ALS) trials with chromosome 9 open reading frame 72 (C9orf72) or superoxide dismutase 1 (SOD1) transcripts as the ASO targets put a spotlight on nontrivial complexities in the deployment of this technology [126,127,128]. This evidence concerns the gene SOD1 and Huntington disease.