9 results about "Dicer" patented technology

The present invention provides oligonucleotides referred to as circular prodrug nucleic acid (“CPN”) as described herein, compositions comprising same, and methods of using same. This design of circular prodrug nucleic acids maintains a circular form until the circularizing domain is cleaved in situ by RNase H or Dicer or other intracellular factors.

Nanoparticulate pharmaceutical formulations and methods for co-delivery of two or more species of nucleic acids for simultaneous suppression and expression of target genes in a cell, are provided. The nanoparticles encapsulate two or more nucleic acid species. The first nucleic acid suppresses expression of a gene or product thereof, e.g., inhibitory nucleic acid, such as antisense, siRNA, miRNA, Dicer siRNA, piRNA, etc. The second nucleic acid increases expression of, or encodes, an endogenous or exogenous protein or polypeptide, e.g., an mRNA. The first and second nucleic acid species simultaneously target or affect the same or different cellular processes within a cell including communication, senescence, DNA repair, gene expression, metabolism, necrosis, and apoptosis.

The present invention provides oligonucleotides referred to as cyclic prodrug nucleic acids ("CPNs") as described herein, compositions comprising the oligonucleotides, and methods of using the same. The design of the annular prodrug nucleic acid keeps annular until the annular structural domain is cut in situ by RNA enzyme H or Dicer or other intracellular factors.

Provided herein are methods, compositions and systems comprising synthetic nucleic acid molecules that enable inducible or conditional pri-miRNA processing, preferably in mammalian cells in vivo. Provided herein are synthetic nucleic acid molecules referred to as Orthogonal RNA Interference induced by Trigger RNA (ORIENTR) that switches between an inactive form and an active form upon interaction with one or more specific RNA-trigger molecules, which can be e.g., a synthetic RNA-trigger, or a disease-specific RNA signals, such as disease-specific mRNA, miRNA, or other cellular RNA products with sequences that characterize a disease state of a cell. The interaction between the RNA-trigger molecules and the ORIENTR is preferably mediated by hybridization, which exposes, facilitates the formation, and / or allows the formation of a correctly folded pri-miRNA scaffold substrate that can be processed by proteins of the RNAi pathway (such as Dicer), leading to RNAi-mediated repression of a target gene. Also provided herein are methods of using such ORIENTR molecules for the treatment or prevention of a disease in a subject, as well as detecting the presence or absence of a target RNA in a biological sample or in vivo.

RNA drug targets are pervasive in cells but methods to design small molecules that target them are sparse. Herein, we report a general approach to score the affinity and selectivity of RNA motif-small molecule interactions identified via selection. Named High Throughput Structure-Activity Relationships Through Sequencing (HiT-StARTS), HiT-StARTS is statistical in nature and compares input nucleic acid sequences to selected library members that bind a ligand via high throughput sequencing. The approach allowed facile definition of the fitness landscape of hundreds of thousands of RNA motif-small molecule binding partners. These results were mined against folded RNAs in the human transcriptome and identified an avid interaction between a small molecule and the Dicer nuclease-processing site in the oncogenic microRNA (miR)-18a hairpin precursor, which is a member of the miR-17-92 cluster. Application of the small molecule, Targapremir-18a, to prostate cancer cells inhibited production of miR-18a from the cluster, de-repressed serine / threonine protein kinase 4 protein (STK4), and triggered apoptosis. Profiling the cellular targets of Targapremir-18a via Chemical Cross Linking and isolation by Pull Down (Chem-CLIP), a covalent small molecule-RNA cellular profiling approach, and other studies showed specific binding of the compound to the miR-18a precursor, revealing broadly applicable factors that govern small molecule drugging of non-coding RNAs.

The present invention relates to a DICER cleavage site motif that is a sequence determinant of dsRNA processing by DICER. Using the DICER cleavage site motif according to the present invention can strongly promote the processing of dsRNA by DICER, and thereby promote RNA interference. In addition, the DICER cleavage site motif according to the present invention is an integrated and conserved determinant of substrate recognition by DICER, and can be applied to any technique capable of generating siRNA through DICER processing. Thus, the present invention can greatly contribute to future studies using DICER processing, for example, studies on the biological or therapeutic use of small RNAs.

The present invention relates to a DICER cleavage site motif that is a sequence determinant of dsRNA processing by DICER. Using the DICER cleavage site motif according to the present invention can strongly promote the processing of dsRNA by DICER, and thereby promote RNA interference. In addition, the DICER cleavage site motif according to the present invention is an integrated and conserved determinant of substrate recognition by DICER, and can be applied to any technique capable of generating siRNA through DICER processing. Thus, the present invention can greatly contribute to future studies using DICER processing, for example, studies on the biological or therapeutic use of small RNAs.

Provided is a method for administering a single RNAi molecule or a combinatorial RNAi molecule via a polycistronic RNAi scaffold, where the polycistronic RNAi scaffold comprises one or more arms disposed on the polycistronic RNAi scaffold, wherein each of the one or more arms is an individual RNAi substrate, where at least one of the one or more arms comprise one or more of: a dicer independent loop sequence, a dicer independent loop-closing sequence, and a corresponding complement sequence. Further, at least one of the one or more arms may further comprise one or more of: an Ago2 cleavage sequence, a corresponding seed sequence, and a MID domain tight interaction.

The present invention provides oligonucleotides referred to as cyclic prodrug nucleic acids ("CPNs") as described herein, compositions comprising the same, and methods of using the same. This design of cyclic prodrug nucleic acids maintains its cyclic form until the cyclic domain is cleaved in situ by RNase H or Dicer or other intracellular factors.