The disclosure provides multimeric oligonucleotide compounds, comprising two or more target-specific oligonucleotides (e.g., antisense oligonucleotides (ASOs)), each being resistant to cleavage, and linked together by a cleavable linker. In particular, two or more linked target-specific oligonucleotides, each to a different target, allows concomitant inhibition of multiple genes' expression levels, while exhibiting favorable pharmacokinetic and pharmacodynamic properties. Methods of making and uses of the described compounds are also provided.

Certain embodiments provide RNA nanostructure (e.g., comprising one single-stranded RNA (ssRNA) molecule, wherein the RNA nanostructure comprises at least one paranemic cohesion crossover), as well as compositions and methods of use thereof. In certain embodiments, such RNA nanostructures are immuno-modulatory (e.g., immuno-stimulatory).

Long interfering nucleic acid (iNA) duplexes, which are at least 30 nucleotides in length, which have at least one nick or nucleotide gap in the antisense or the sense strands or in both the sense and antisense strands. These long iNA duplexes do not induce an interferon response when transfected into mammalian cells. The antisense strands can target two separate mRNAs or two segments of one mRNA.

The instant invention provides RNA nanocubes, DNA nanocubes and R/DNA chimeric nanocubes comprising one or more functionalities. The multifunctional RNA nanocubes are suitable for therapeutic or diagnostic use in a number of diseases or disorders.

Provided is an aptamer including a polynucleotide of any of the following (a) to (c) and capable of binding to an HGF receptor to exhibit an activity of inhibiting the binding of HGF to the HGF receptor. (a) A polynucleotide consisting of a base sequence set forth in SEQ ID NO: 1, (b) A polynucleotide consisting of a base sequence having the deletion, substitution, insertion and/or addition of one to several bases in the base sequence set forth in SEQ ID NO: 1, and (c) A polynucleotide consisting of a base sequence having a sequence identity of 80% or more to the base sequence set forth in SEQ ID NO: 1.

Methods, and kits for inducing cell death in proliferating cells as well as methods of treating cancer, are provided. In some embodiments, the methods comprise administering a composition comprising a replication competent retrovirus (RCR) comprising an antisense molecule that targets a hypoxia-inducible gene including but not limited to HIF-1 and CREB, and anti-cancer therapy.

Described herein are immuno-stimulatory RNA nanostructures (which comprises a single-stranded RNA (ssRNA) molecule, wherein the ssRNA molecule forms at least one paranemic cohesion crossover), as well as compositions and methods of use thereof.

Nucleic acid molecules such as shRNA clusters and artificial miRNA clusters are disclosed, Also disclosed are methods of use, compositions, cells, viral particles, and kits relating to the nucleic acid molecules disclosed herein. The disclosure provides, at least in part nucleic acid molecules such as shRNA clusters encoding shRNA-like molecules and artificial miRNA clusters encoding modified pri-miRNA-like molecules. The shRNA clusters and artificial miRNA clusters disclosed herein can be used, for example, to produce artificial RNA molecules, e.g., RNAi molecules. Cells, viral particles, compositions (e.g., pharmaceutical compositions), kits, and methods relating to the nucleic acid molecules, e.g., shRNA clusters and artificial miRNA clusters, are also disclosed. The nucleic acid molecules (e.g., shRNA clusters and artificial miRNA clusters), artificial RNA molecules (e.g., RNAi molecules), cells, viral particles, compositions (e.g., pharmaceutical compositions), and kits and methods disclosed herein can be used to treat or prevent a disease, e.g., HIV infection and/or AIDS.

The instant invention provides polyvalent RNA nanoparticles comprising RNA motifs as building blocks that can form RNA nanotubes. The polyvalent RNA nanoparticles are suitable for therapeutic or diagnostic use in a number of diseases or disorders.

Materials and methods related to using short DNA aptamers to treat demyelinating diseases are provided herein.