Universal nucleic acid binding molecules (e.g., antisense oligonucleotides or RNAi molecules) having an inhibitory or activating nucleic acid sequence which binds a receiving nucleic acid sequence (e.g., RNA or DNA) are provided. In some embodiments, the universal nucleic acid binding molecules bind the receiving nucleic acid sequence (e.g., RNA or DNA) via at least one non-Watson Crick or non-canonical paired base.

The present invention is directed to antisense oligomeric compounds that may be used in the treatment Pompe disease as well as method for modulating the splicing of the GAA gene and method to treat Pompe disease. Also pharmaceutical compositions comprising the antisense oligomeric compounds are part of the invention.

CRISPR/CAS-related compositions and methods for treatment of Sickle Cell Disease (SCD) are disclosed.

The current invention provides an improved oligonucleotide and its use for treating, ameliorating, preventing, delaying and/or treating a human cis-element repeat instability associated genetic neuromuscular or neurodegenerative disorder.

The present invention relates to treatment of inflammatory bowel disease (e.g., Crohn's disease and ulcerative colitis) using antisense nucleotides that are directed against polymorphic forms (e.g., those containing single nucleotide polymorphisms) of the SMAD7 mRNA. The invention thus relates to treatment methods for subjects having polymorphic forms of SMAD7 and antisense oligonucleotides that specifically target SMAD7 mRNA transcripts containing polymorphisms.

Provided are human miRNAs associated with the generation of immunological tolerance during pregnancy as well as fragments, derivatives and variants thereof for use in immunomodulation. Said miRNAs may be used in diagnosis and treatment of disorders associated with a deregulated immune response, autoimmune disorders, pregnancy associated diseases, failure or problems of placentation and complications resulting from allotransplantations. In addition, new pharmaceutical and diagnostic compositions for use in diagnosis and therapy of said disorders are described.

Provided herein are compositions and methods for reducing expression of C9orf72 transcripts in cells containing expanded intronic GGGGCC regions, including those in subjects having or at risk of developing amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Provided herein are a double-stranded oligonucleotides of 13 to 22 nucleobases in length targeting a GGGGCC expanded repeat region in an intron of C9orf72, comprises (a) 3-5 central mismatches (within bases 9-14) within a target sequence comprising the expanded repeat sequence, or (h) 3-5 mismatches outside of the seed sequence (bases 2-8 within the guide strand complementary to the expanded repeat sequence).

Aspects of the disclosure relate to methods and compositions useful for treating bestrophinopathies, such as Best Disease.

The present disclosure provides methods of treating subjects having a liver disease, and methods of identifying subjects having an increased risk of developing a liver disease.

Disclosed are oligonucleotides which target and hybridize to nucleic acid molecules encoding FGFR3, leading to reduced expression of FGFR3. Reduction in the aberrant expression of FGFR3 is beneficial for the treatment of certain medical disorders, such as achondroplasia.