The invention provides compositions and methods for nucleic acid synthesis, including ordered and continuous complementary DNA (cDNA) synthesis across non-continuous templates using a modified eukaryotic non-long terminal repeat reverse transcriptase (non-LTR RT) protein.

Disclosed herein are compounds and methods for modulating C9orf72 transcript. Such compounds and methods are useful to treat, prevent, or ameliorate neurodegenerative diseases in an individual in need thereof.

This invention relates to compounds, compositions, and methods useful for reducing AT3 target RNA and protein levels via use of dsRNAs, e.g., Dicer substrate siRNA (DsiRNA) agents.

Certain embodiments are directed to methods and compounds for inhibiting SMN-NAT, the natural antisense transcript of SMN. Such methods and compounds are useful for increasing expression of SMN in cells and animals

The present invention relates to chemical modification motifs for oligonucleotides. The oligonucleotides of the present invention, such as chemically modified antisense oligonucleotides, can have increased in vivo efficacy. The chemically modified oligonucleotides provide advantages in one or more of potency, efficiency of delivery, target specificity, toxicity, and/or stability. The chemically modified oligonucleotides have a specific chemical modification motif or pattern of locked nucleic acids (LNAs). The oligonucleotide (e.g. antisense oligonucleotide) can target RNA, such as miRNA or mRNA. Also provided herein are compositions comprising the chemically modified oligonucleotides and methods of using the chemically modified oligonucleotides as therapeutics for various disorders, including cardiovascular disorders.

Provided herein are multi-valent oligonucleotide agents comprising two or more functional oligonucleotide units independently selected from single-stranded antisense oligonucleotides (ASOs, such as gapmers, mixmers and steric block ASOs) and duplex (double-stranded) RNAs (dsRNAs, such as siRNA and saRNA), and methods for the preparation thereof. Also provided herein are products, comprising the multi-valent oligonucleotide agents, and methods of using the multi-valent oligonucleotide agents or products in treatment of diseases (such as spinal muscular atrophy (SMA) and cancers).

Disclosed herein are antisense compounds and methods for decreasing Ataxin 2 mRNA and protein expression. Such methods, compounds, and compositions are useful to treat, prevent, or ameliorate Ataxin 2 associated diseases, disorders, and conditions. Such Ataxin 2 associated diseases include spinocerebellar ataxia type 2 (SCA2), amyotropic sclerosis (ALS), and parkinsonism.

The present invention relates to PIKFYVE antisense oligonucleotides (ASOs), pharmaceutical compositions containing them, and methods for treating, inhibiting, suppressing, and preventing neurological diseases with them.

The present embodiments provide methods, compounds, and compositions useful for inhibiting ENaC expression, which may be useful for treating, preventing, or ameliorating a disease associated with ENaC.

Disclosed herein are antisense compounds and methods for decreasing Tau mRNA and protein expression. Such methods, compounds, and compositions are useful to treat, prevent, or ameliorate Tau-associated diseases, disorders, and conditions.