One aspect of the present invention relates to an oral formulation for reducing or inhibiting the expression of a target gene in a subject, comprising a) double stranded iRNA agent comprising an antisense strand which is complementary to a target gene; a sense strand which is complementary to said antisense strand; 2′-OMe modifications to more than fifteen, more than twenty, more than twenty-five, or more than thirty nucleotides; and a carbohydrate-based ligand conjugated to at least one strand, optionally via a linker or carrier; and b) a penetration enhancer. Another aspect of the invention relates to a method of gene silencing, comprising orally administering to a subject in need thereof the oral formulation.

Disclosed herein are immunotherapeutic constructs comprising a delivery particle, at least one adjuvant, and one or more therapeutic agents/compounds that cause antigen release and/or modulate immunosuppressive tumor microenvironment. These immunotherapeutic constructs create adaptive immunity or anti-cancer immune response(s) that can be used, for instance, to prevent and treat broad types of cancer. Further disclosed are uses of the immunotherapeutic constructs, including to prevent and treat cancer in humans and animals.

Disclosed herein are engineered oligonucleotides for selective inhibition of polypeptide expression and activity. Also disclosed herein are methods of selectively inhibiting polypeptide expression and activity contacting an engineered oligonucleotide with a polynucleotide encoding the polypeptide.

Disclosed herein are engineered oligonucleotides for selective inhibition of polypeptide expression and activity. Also disclosed herein are methods of selectively inhibiting polypeptide expression and activity contacting an engineered oligonucleotide with a polynucleotide encoding the polypeptide.

The present disclosure features useful compositions and methods to treat nucleotide repeat expansion disorders, e.g., in a subject in need thereof. In some aspects, the compositions and methods described herein are useful in the treatment of disorders associated with MSH3 activity.

The present disclosure provides a composition containing a purified and enriched population of potent exosomes derived from extracellular vesicles derived from mesenchymal stem cells (MSCs), a method for diagnosing a human subject aged over 50 years with an age-related chronic disease characterized by disease related dysfunction and optimally treating the subject, and a method for reprogramming a donated organ or tissue comprising a fibrotic disposition including treating the donated organ or tissue with a composition comprising purified enriched population of potent exosomes derived from extracellular vesicles derived from MSCs of a normal healthy subject.

Methods for treating muscular dystrophy by administering a pharmaceutical composition comprising about 80 to about 300 mg/kg of an antisense oligomer, or pharmaceutically acceptable salt thereof, are described. In one embodiment, the compositions are administered less frequently than occurs in existing methods of treatment

This invention provides compositions for use in distributing active agents for treating a malignant tumor in a subject. The compositions contain RNAi molecules targeted to a human GST-π, along with RNAi molecules targeted to a human p21, and a pharmaceutically acceptable carrier. The carrier can include nanoparticles composed of an ionizable lipid, a structural lipid, one or more stabilizer lipids, and a lipid for reducing immunogenicity of the nanoparticles. This invention further provides methods for preventing or treating a malignant tumor by administering a therapeutically effective amount of an RNAi composition.

Aspects of the invention relate to methods for treating cancer by administering to a subject in need thereof a therapeutically effective amount of a nucleic acid molecule that is directed against a gene encoding mouse double minute 1 homolog (MDM1), mouse double minute 2 homolog (MDM2), mouse double minute 3 homolog (MDM3), mouse double minute 4 homolog (MDM4) or V-myc myelocytomatosis viral related oncogene (MYCN) for treating cancer. Further aspects of the invention relate to nucleic acid molecules and compositions comprising nucleic acid molecules.

Provided herein are methods for oral administration of oligonucleotides. Further provided herein are methods for oral administration of modified oligonucleotides targeted to microRNA.