Abstract: Gapmers or pharmaceutically acceptable salt of the gapmers and methods of making the gapmers are provided. The gapmers include a gap region that contains deoxyribonucleosides linked to each other by phosphorothioate bonds, a 5? wing region positioned at the 5? end of the gap region that contains morpholino monomers linked to each other by phosphorodiamidate bonds, and a 3? wing region positioned at the 3? end of the gap region that contains morpholino monomers linked to each other by phosphorodiamidate bonds. Antisense oligonucleotides are also provided. These antisense oligonucleotides are useful in the preparation of gapmers for inhibition of Tau mRNA transcription.