An object of the present invention is to provide a convenient and low-cost method for enhancing the stability of a DNA aptamer and/or its capacity to bind to a target molecule, and DNA aptamer obtained by the method.

The object is solved by substituting an internal hairpin structure (stem-loop structure) of the DNA aptamer with a structure called mini-hairpin structure and optionally increasing GC pairs in a stem portion of the DNA aptamer.

The invention provides compositions and methods for reducing expression of a target gene in a cell, involving contacting a cell with an isolated double stranded nucleic acid (dsNA) in an amount effective to reduce expression of a target gene in a cell. The dsNAs of the invention possess a pattern of deoxyribonucleotides (in most embodiments, the pattern comprises at least one deoxyribonucleotide-deoxyribonucleotide base pair) designed to direct the site of Dicer enzyme cleavage within the dsNA molecule. Deoxyribonucleotides of the dsNA molecules of the invention are located within a region of the dsNA that can be excised via Dicer cleavage to generate an active siRNA agent that no longer contains the deoxyribonucleotide pattern (e.g., deoxyribonucleotide-deoxyribonucleotide base pairs). Such DNA-extended Dicer-substrate siRNAs (DsiRNAs) were demonstrated to be more effective RNA inhibitory agents than corresponding double stranded RNA-extended DsiRNAs. DsiRNA agents were also found to tolerate guide strand mismatches.

A method of reducing the level of a transcription product in a cell comprising contacting with the cell a composition comprising a double-stranded nucleic acid complex comprising a first nucleic acid strand annealed to a second nucleic acid strand, wherein: (i) the first nucleic acid strand hybridizes to the transcription product and comprises (a) a region consisting of at least 4 consecutive nucleotides that are recognized by RNase H when the strand is hybridized to the transcription product, (b) one or more nucleotide analogs located on 5 terminal side of the region, (c) one or more nucleotide analogs located on 3 terminal side of the region and (d) a total number of nucleotides and nucleotide analogs ranging from 8 to 35 nucleotides and (ii) the second nucleic acid strand comprises (a) nucleotides and optionally nucleotide analogs and (b) at least 4 consecutive RNA nucleotides.

Disclosed are polynucleotides, compositions, and methods related to RNA interference (RNAi). The disclosed polynucleotides, compositions, and methods may be utilized for treating diseases and disorders through RNAi. Particular disclosed are toxic RNAi active seed sequences and methods of using toxic RNAi active sequences for killing cancer cells. The disclosed toxic RNAi active seed sequences preferentially target and inhibit the expression of multiple essential genes for cell survival and/or growth through a process called death-induced by survival gene elimination or DISE.

The invention relates to compositions and methods for the preparation, manufacture and therapeutic use of modulatory polynucleotides.

Disclosed are compositions and methods related to RNA interference (RNAi) and the use of RNAi active sequence for treating diseases and disorders. Particular disclosed are toxic RNAi active sequences such as siRNA and shRNA for killing cancer cells. The disclosed toxic RNAi active sequences typically include trinucleotide repeats and preferentially target the expression of multiple essential genes for cell survival and/or growth.

The present invention provides novel bicyclic carbocyclic nucleosides and oligomeric compounds prepared therefrom. Incorporation of one or more of the bicyclic carbocyclic nucleosides into an oligomeric compound is expected to enhance one or more properties of the oligomeric compound. In certain embodiments, the oligomeric compounds provided herein hybridize to a portion of a target RNA resulting in modulation of normal function of the target RNA. In certain embodiments, bicyclic carbocyclic nucleosides are provided as monomers for use as antivirals.

The invention generally relates to isolated nucleic acid ligands that are neutral under physiological conditions.

The invention relates in aspects to hybrid RNAs lacking a poly-A tail and nucleic acid vectors for expressing the RNA. The hybrid RNAs in some instances have a stabilizing triple helical structure. Related methods for expressing RNA in vivo and in vitro are also disclosed.

The present invention relates to RNAi constructs with improved tissue and cellular uptake characteristics and methods of use of these compounds in dermal and fibrotic applications.