The present disclosure describes short antisense compounds, including such
compounds comprising chemically-modified high-affinity monomers 8-16
monomers in length. Certain such short antisense compound are useful for
the reduction of target nucleic acids and/or proteins in cells, tissues,
and animals with increased potency and improved therapeutic index. Thus,
provided herein are short antisense compounds comprising high-affinity
nucleotide modifications useful for reducing a target RNA in vivo. Such
short antisense compounds are effective at lower doses than previously
described antisense compounds, allowing for a reduction in toxicity and
cost of treatment. In addition, the described short antisense compounds
have greater potential for oral dosing.