The present invention provides an oligonucleotide which is capable of activating RIG-I and inducing an anti-viral, in particular, an IFN, response in cells expressing RIG-I. The present invention further provides an oligonucleotide which is capable of activating RIG-I and which has target gene-silencing activity. The oligonucleotide of the present invention has a double-stranded section of at least 19, preferably at least 21 bp, at least one 5′ triphosphate, and at least one blunt end which bears a 5′ triphosphate. The present invention further provides the use said oligonucleotide for inducing an anti-viral, in particular, an IFN, response in vitro and in vivo. The present invention additionally provides the use of said oligonucleotide for preventing and/or treating diseases or conditions such as infections, tumors/cancers, and immune disorders.

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.

The invention provides immunomodulatory polynucleotides and methods for immunomodulation of individuals using the immunomodulatory polynucleotides.

This disclosure provides improved lipid-based compositions, including lipid nanoparticle compositions, and methods of use thereof for delivering agents in vivo including nucleic acids and proteins. These compositions are not subject to accelerated blood clearance and they have an improved toxicity profile in vivo.

The invention provides therapeutic combinations and therapeutic methods that are useful for treating hepatitis B.

Aptamers that bind to and antagonize PD-1 and uses thereof in promoting T cell proliferation, treating cancer or infectious diseases such as HIV infection.

Provided are production methods capable of controlling quality of a bifurcated lipid-linked oligonucleotide, and intermediates which is useful for the production method, has good stability, and is easy to manage and analyze. Specifically, it is a method for producing a bifurcated lipid-linked oligonucleotide including a step of reacting a compound of formula (II):

##STR00001## wherein Pro.sup.1 to Pro.sup.4 are each independently a protecting group; Pro.sup.1 and Pro.sup.2 or Pro.sup.3 and Pro.sup.4 may be taken together to form a protecting group; m, n and p are each independently an integer of 0 to 5; and Y is a group of a formula: —P(OC.sub.2H.sub.4CN)(N(i-Pr).sub.2), or the like, with an oligonucleotide.

Methods of treating Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD), comprising administering an inhibitory nucleic acid that targets miR-128.

The invention provides a method for the prophylaxis or treatment of hepatitis C in a mammal with a peptide-bound liposome wherein the peptide contains a partial amino acid sequence having a length of not less than 9 amino acids in the amino acid sequence of hepatitis C virus NS3 protein, has a length of 9 to 11 amino acids, and is capable of inducing cytotoxic T lymphocytes; the liposome contains a phospholipid containing an acyl group having 14 to 24 carbon atoms and one unsaturated bond or a hydrocarbon group having 14 to 24 carbon atoms and one unsaturated bond, and a liposome stabilizer; and the peptide is bound to the surface of the liposome. The invention also provides a cytotoxic T lymphocyte activator containing the peptide-bound liposome, as well as a hepatitis C virus vaccine.

The invention provides a double-stranded ribonucleic acid (dsRNA) having a chain length suitable for simultaneously showing low toxicity and high function in the use of an adjuvant and the like, and resisting variation of chain length even when subjected to a heating and cooling treatment, or a salt thereof; an immune potentiator, adjuvant, pharmaceutical product and the like containing the dsRNA and the like; and a production method of such dsRNA and the like. The invention is characterized in that the weight average chain length of two or more single-stranded ribonucleic acids (ssRNAs) constituting the first chain constituting dsRNA is not more than ½ of the weight average chain length of one ssRNA constituting the second chain.