The present invention provides antisense oligonucleotides directed against immune checkpoints and methods and compositions of using such antisense oligonucleotides for the treatment of cancer.

The present disclosure provides oligomeric compounds. Certain such oligomeric compounds are useful for hybridizing to a complementary nucleic acid, including but not limited, to nucleic acids in a cell. In certain embodiments, hybridization results in modulation of the amount activity or expression of the target nucleic acid in a cell.

In certain embodiments, the present disclosure provides methods comprising contacting a cell with a compound comprising a modified oligonucleotide complementary to a nucleic acid transcript. In certain such embodiments, the modified oligonucleotide does not interact or interacts poorly with a mRNP complex or granule. In certain such embodiments the modifications and/or motifs of the modified oligonucleotide do not promote interaction with a mRNP complex or granule. In certain embodiments, the present disclosure provides methods comprising contacting a cell with a compound comprising a modified oligonucleotide thereby reducing the size or amount of protein aggregation in the cell. In certain such embodiments, the protein aggregate is a mRNP granule. In certain such embodiments, the modifications and/or motifs of the modified oligonucleotide promote interaction with a protein aggregate, such as a mRNP granule, that results in disruption of the protein aggregate.

The present disclosure provides antisense compounds, methods, and compositions for silencing ADAM33 mRNA. The present disclosure provides antisense compounds, methods, and compositions for the treatment, prevention, or amelioration of diseases, disorders, and conditions associated with ADAM33 in a subject in need thereof. Also contemplated are antisense compounds and methods for the preparation of a medicament for the treatment, prevention, or amelioration of a disease, disorder, or condition associated with ADAM33.

The present disclosure provides antisense compounds, methods, and compositions for silencing ADAM33 mRNA. The present disclosure provides antisense compounds, methods, and compositions for the treatment, prevention, or amelioration of diseases, disorders, and conditions associated with ADAM33 in a subject in need thereof. Also contemplated are antisense compounds and methods for the preparation of a medicament for the treatment, prevention, or amelioration of a disease, disorder, or condition associated with ADAM33.

Disclosed is a method of treating a subject who has a neurological disease. The neurological disease may be associated with altered C9ORF72 protein activity. In one aspect, the method includes a step of administering an effective dose of a PIKFYVE antisense or inhibitory nucleic acid to a subject in need thereof, thereby rescuing the defects associated with altered C9ORF72 protein activity and/or inhibiting the expression of PIKFYVE gene.

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

The present invention relates to nucleic acid molecules that are complementary to both PAP associated domain containing 5 (PAPD5) and PAP associated domain containing 7 (PAPD7), leading to inhibition of the expression of both PAPD5 and PAPD7 when using a single nucleic acid molecule. The invention also provides for PAPD5 and PAPD7 specific nucleic acid molecules for use in treating and/or preventing a HBV infection, in particular a chronic HBV infection. Also comprised in the present invention is a pharmaceutical composition for use in the treatment and/or prevention of a HBV infection.

The present invention relates to oligonucleotides that are complementary to and modulate the expression of TMEM106B. The present invention further relates to conjugates of the oligonucleotide and pharmaceutical compositions and methods for treatment of neurological disorders using the oligonucleotide.

The present invention relates to the use of an antisense oligonucleotide targeting LINC00518 for the treatment of melanoma.