The disclosure relates to double stranded ribonucleic acid (dsRNAi) agents and compositions targeting a Huntingtin (HTT) gene, e.g., exon 1 of an HTT gene, as well as methods of inhibiting expression of an HTT gene and methods of treating subjects having an HTT-associated disease or disorder, e.g., Huntington's disease, using such dsRNAi agents and compositions.

Described are compounds and methods useful in the treatment of Fuchs' Endothelial Corneal Dystrophy (FECD).

Disclosed herein are compositions and methods comprising extracellular vesicles comprising nucleic acid that target genes, leading to macrophage polarization of tumor associated macrophages. In certain embodiments, disclosed herein are methods and compositions for increasing macrophage polarization for the treatment of cancer.

The present disclosure relates to double-stranded oligonucleotides, including double-stranded oligonucleotides such as siRNAs, comprising a sense strand oligonucleotide and an antisense strand oligonucleotide, and wherein the antisense strand oligonucleotide comprises one or more nucleotide analogs of formula (I-A) which are neither the 5′-overhang nucleotide nor the 3′-overhang nucleotide of the said antisense strand oligonucleotide, and wherein a nucleotide analog of formula (I-A) is as described in the disclosure. Oligonucleotides containing these analogs have superior biological activity, for example, increased in vitro stability and improved in vivo potency especially improved off-target profiles. The improved oligonucleotides are useful for silencing (e.g., reducing or eradicating) the expression of a target gene.

Disclosed herein are inhibitors of PPM 1 A, including PPM1A antisense oligonucleotide sequences, and methods for treating neurological diseases, such as amyotrophic lateral sclerosis and frontotemporal dementia, associated with decreased activity or expression of TBK1. Also disclosed are pharmaceutical compositions containing a PPM1A inhibitor, including a PPM1A antisense oligonucleotide, useful for treating neurological diseases and manufacture of medicaments containing a disclosed PPM1A inhibitor, for example, a PPM1A antisense oligonucleotide, to be used in treating a neurological disease

The present invention relates to an oligomer conjugate for use in the treatment of a viral disorder. The oligomer conjugate comprises: a) an oligomer capable of modulating a target sequence in HBx and/or HBsAg of Hepatitis B Virus (HBV) to treat said viral disorder; and b) a carrier component capable of delivering the oligomer to the liver which is linked, preferably conjugated, to the oligomer.

In one aspect, the invention relates to a method of loading exosomes with oligonucleotide cargo, by incubating an oligonucleotide comprising one or more hydrophobic modifications with a population of exosomes for a period of time sufficient to allow loading of the exosomes with the oligonucleotide. Exosomes loaded with hydrophobically modified oligonucleotide cargo, and uses thereof, are also provided.

Amphiphilic oligonucleotide conjugates that enhance adjuvant function are disclosed. The conjugates typically include: a lipophilic component, and conjugated thereto (directly or indirectly) an immunomodulating oligonucleotide that, if it were not conjugated to the lipophilic component, would suppress TLR7 and/or TLR8 stimulation. In the presence of albumin, these conjugates significantly enhance adjuvant function, in particular the function of TLR7/8-mediated adjuvants such as an imidazoquinolinamine. The conjugates can be administered, along with an adjuvant compound, to a subject in order to cause and/or enhance an immune response (for instance, to an infectious agent or a cancer antigen) in the subject.

The invention relates to a double-stranded ribonucleic acid (dsRNA) targeting a mutant Epidermal Growth Factor Receptor (EGFR), and methods of using the dsRNA to inhibit expression of mutant EGFR.

The disclosure relates to double-stranded ribonucleic acid (dsRNA) agents and compositions targeting the ATXN3 gene, as well as methods of inhibiting expression of an APP gene and methods of treating subjects having an ATXN3-associated disease or disorder, such as SCA3, using such dsRNA agents and compositions.