CRISPR complex for efficient RNA knockdown; plus improving ASOs for SMA and more

Jennifer Doudna, David Colognori and Marena Trinidad from University of California Berkeley posted a bioRxiv preprint describing a CRISPR-Csm complex that can target and degrade nuclear and cytoplasmic transcripts in human cells with higher efficiency than current RNA knockdown technologies such as shRNA and Cas13. The Csm system, from Streptococcus thermophilus, resulted in 10-fold fewer off-target effects than Cas13 and, unlike RNAi, can target nuclear noncoding RNAs and pre-mRNAs. The authors believe the technology “has important implications for development of synthetic circuits, RNA diagnostics and reporter assays/screens in vivo.”

A team led by Alberto Kornblihtt at  University of Buenos Aires showed in Cell the histone deacetylase inhibitor valproic acid counteracts the chromatin silencing effects of an antisense oligonucleotide (ASO) similar to Spinraza nusinersen, which modulates splicing of SMN2 mRNA. Combined administration of a nusinersen-like ASO and valproic acid enhanced growth, survival and neuromuscular function in mice with spinal muscular atrophy compared with the ASO alone. Coauthor Adrian Krainer is an inventor on nusinersen patents licensed by Cold Spring Harbor Laboratory to Ionis Pharmaceuticals Inc. (NASDAQ:IONS), and sublicensed to  Biogen Inc. (NASDAQ:BIIB)...