The invention pertains to modifications for antisense oligonucleotides, wherein the modifications are used to improve stability and provide protection from nuclease degradation. The modifications could also be incorporated into double-stranded nucleic acids, such as synthetic siRNAs and miRNAs.

One aspect of the invention relates to molecules that target more than one target nucleic acid sequence and that exhibit efficacy in the tissues of the CNS of a subject upon contact. Another aspect of the present invention relates to a small circular interfering RNA (sciRNA) for modulating one or more target mRNAs in the central nervous system (CNS) of a subject. Other aspects of the invention relate a pharmaceutical composition, a method for inhibiting the expression of one or more target mRNAs in the CNS of a subject, and a method of treating or preventing a CNS disease or disorder in a subject using the molecules and sciRNA.

Modified oligonucleotides comprising a GalNAc moiety of the present disclosure along with methods of making and use, e.g., against HBV are disclosed.

The present disclosure relates to the preparation and use of CAR-NK cells which are modified by a nucleic acid targeting compound.