The present invention relates to a multi siRNA complex with increased intracellular transmission capacity and a multi-functional nucleic acid structure complex. The siRNA complex and multi-functional nucleic acid structure complex according to the invention have the advantage of having a novel structure that enables easier chemical synthesis compared to the existing shRNA system used to inhibit expression of a plurality of target genes and also enabling the inhibition of the expression of a plurality of genes at enhanced efficiencies compared to the existing siRNA. In addition, because it has high intracellular transmission capacity and also enables inhibition of the expression of target genes specifically without incurring non-specific antiviral reactions, it is very useful as the therapeutic agent mediated by the siRNA mechanism to treat cancer or viral infection. Furthermore, the multifunctional nuclei acid structure complex according to the invention can combine with functional nucleic acid oligonucleotides such as miRNA, antagomiR, antisense oligonucleotide, aptamer and ribozyme, in addition to siRNA, to provide diverse functionality.

The presently-disclosed subject matter relates to RNA-based composition and method to treat breast cancer in a subject. More particularly, the presently disclosed subject matter relates to a RNA nanostructure and composition containing a multiple branched RNA nanoparticle, a breast cancer targeting module, and an effective amount of a breast cancer therapeutic agent. Further, the presently disclosed subject matter relates to a method of using the RNA nanoparticle composition to treat breast cancer in a subject having or at risk of having breast cancer.

The presently-disclosed subject matter relates to an artificial RNA nanostructure molecule and method to treat brain tumor in a subject. More particularly, the presently disclosed subject matter relates to a RNA nanostructure containing a multiple branched RNA nanoparticle, a brain tumor targeting module, and an effective amount of a therapeutic agent. Further, the presently disclosed subject matter relates to a method of using the RNA nanostructure composition to treat brain tumor in a subject having or at risk of having brain tumor.

The present disclosure provides engineered polynucleotide sequences that form scaffolds and nucleoprotein complexes comprising such engineered polynucleotide sequences that form scaffolds and nucleic acid binding proteins. Nucleic acid sequences encoding the engineered polynucleotide sequences that form scaffolds, as well as expression cassettes, vectors and cells comprising such polynucleotide sequences, are described. A variety of methods for making and using the engineered polynucleotide sequences that form scaffolds are also disclosed.

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

The present invention is directed to novel self-forming polynucleotide nanoparticles, and the use of such nanoparticles and compositions comprising the same for gene modulation in a variety of organisms.

Three-way junction (3WJ) RNA scaffolds derived from phi29, M2, SF5, and GA1 pRNAs and which have high stability are described. The pRNA 3WJ scaffolds can be used to form compounds, conjugates, compositions, and nanoparticles for delivery of active agents for therapeutic and/or diagnostic functions.

The presently-disclosed subject matter relates to RNA-based composition and method to treat gastric cancer in a subject. More particularly, the presently disclosed subject matter relates to a RNA nanostructure and composition containing a multiple branched RNA nanoparticle, a gastric cancer targeting module, and an effective amount of a therapeutic agent. Further, the presently disclosed subject matter relates to a method of using the RNA nanoparticle composition to treat gastric cancer in a subject having or at risk of having gastric cancer.

The present disclosure provides an RNA oligonucleotide having a helical bend structure and a use thereof. Specifically, double strands formed by a complementary binding of two sequences have a helical bend structure in the RNA oligonucleotide. The RNA oligonucleotide can increase the expression of interferon- or ISG56 and thus can be used as an immune system enhancer.

The present disclosure provides single- or double-stranded therapeutic oligonucleotides (e.g., siRNAs, shRNAs, miRNAs, gRNAs, and ASOs) having a plurality of cationic binding sites that are partially or fully saturated by a plurality of divalent cations (e.g., Ba.sup.2+, Be.sup.2+, Ca.sup.2+, Cu.sup.2+, Mg.sup.2+, Mn.sup.2+, Ni.sup.2+, or Zn.sup.2+, or a combination thereof). The therapeutic oligonucleotides may contain specific patterns of nucleoside modifications and internucleoside linkage modifications, as pharmaceutical compositions including the same. The siRNA molecules may be branched siRNA molecules, such as di-branched, tri-branched, or tetra-branched siRNA molecules. The disclosed siRNA molecules may further feature a 5 phosphorus stabilizing moiety and/or a hydrophobic moiety. Additionally, the disclosure provides methods for delivering the siRNA molecule of the disclosure to the central nervous system of a subject, such as a subject identified as having a disease.