RNA molecules inhibiting a DNMT and methods and compositions incorporating or generating the RNA molecules are described.

The present invention relates to G-quadruplex forming isoDNA aptamers and a process for the preparation thereof. The present invention further relates to a stable, non-genetic, guanine rich 2-5 linked isoDNA selected from 3 deoxy 2-5 isoDNA and 3 deoxy 2-5 isoDNA-isoRNA hybrid. The instant 2-5 linked isoDNA such as the thrombin binding aptamer (isoTBA) can be used in deep vein thrombosis, where prolonged anticoagulant activity is required.

Stable self-assembling nucleic acid nanostructures comprising: a plurality of oligonucleotides, a plurality of G-quadruplex forming nucleic acids linked to the plurality of oligonucleotides, and a plurality of G-quadruplex stabilizing domains linked to the G-quadruplex forming nucleic acids. The nucleic acid nanostructures are suitable for use as agonists or antagonists of nucleic acid interacting complexes, such as Toll-like receptors; for inhibiting DNA or RNA expression; for stimulating or inhibiting an immune response; and for treating diseases such as cancer, infectious diseases, allergies and allergic diseases, and autoimmune diseases.

Quadruplex-forming guanine-rich nucleic acid sequences are useful in compositions and methods for inhibiting cellular growth and proliferation and inducing cell death. Compositions for treating a patient are provided, including (i) a safe and effective amount of a sequence having at least 80% nucleic acid identity with a sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO:3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12 and combinations thereof, and (ii) a carrier, wherein the isolated oligonucleotide forms at least one quadruplex.

The present invention relates to tetramolecular parallel G-quadruplex-forming oligonucleotides. If G-quadruplexes are of prime importance in biology, their use is hampered by the propensity of G4-prone DNA molecules, in particular G4-prone DNA molecules of long size, to adopt many different G4 topological conformations or other alternative foldings. By introducing a lipid modification at the end of the oligonucleotide, the inventors succeeded in obtaining long tetramolecular parallel G-quadruplexes (tpG4). The present invention thus concerns an oligonucleotide modified by substitution at the 5 or the 3 end by a lipid moiety, wherein said oligonucleotide comprises a nucleic acid sequence of at least 10 nucleotides, said nucleic acid sequence including a series of at least 4 consecutive guanine residues located in the middle of said sequence. A tetramolecular parallel G-quadruplex comprising 4 identical modified oligonucleotides as defined above, wherein each of the 4 consecutive guanine residues included in the middle of the nucleic acid sequence of each oligonucleotide respectively form G-quartets with the corresponding guanine residues of the other 3 oligonucleotides, said G-quartets being stabilized by - staking and Hoogsteen hydrogen bonding, is also contemplated.

Described herein are compositions composed of peptide nucleic acid strands. In some aspects the peptide nucleic acid strands are complementary to at least a portion of another peptide nucleic acid strand that may have one or more gamma substituents, where the ratio of PNA strands is least 1:1. Certain gamma substituents are capable of effecting attachment of a PNA strand to a cell. The disclosure also concerns construction of nanostructure platforms and vaccines and use of the inventive compositions in inhibiting disease states in mammals.

Described herein are compositions that may be used to detect viral nucleic acid. For example, these compositions may comprise a DNA-nanostructure, a capture oligonucleotide and a protector oligonucleotide, wherein the components are designed based on a duo-toehold-mediated displacement reaction (duo-TMDR) strategy. In this strategy, a first TMDR can switch off a Faster resonance energy transfer (FRET) process and a second TMDR can release the target viral nucleic acid and amplify the signal. Methods of using such compositions are also provided herein.

Provided herein are compositions and methods involving nucleic acid nanostructures that can encapsulate cargo for use in, for example, therapeutic, diagnostic, and analytical applications. The nanostructures can have a plurality of interconnected subunits configured such that the nanostructures have a continuous torus-like structure with a closed three-dimensional cavity. Preferably, the nanostructure is a nucleic acid mazzocchio. The subunits are connected by linkers having defined lengths to constrain the nanostructure into the continuous torus-like shape. The closed three-dimensional cavity is of defined size to encapsulate any cargo of interest. Cargo can also be positioned in the open hole at the center of the nanostructure. The cargo can be a wide range of compounds including, for example, chemical drugs, small molecules, therapeutics, targeting agents, enzymes, dyes, and fluorescent molecules. As such, the disclosed nanostructures are suitable for delivery of one or more therapeutic, toxic, imaging, diagnostic, or prophylactic agents.