The present specification provides a drug that causes highly-efficient skipping of exon 51 in the human dystrophin gene. The present specification provides an antisense oligomer having an activity to induce skipping of exon 51 in the human dystrophin gene.

A hybrid guide RNA (hgRNA) comprising a proximal spacer, a distal spacer, a type II CRISPR-Cas tracrRNA, and a type V CRISPR-Cas direct repeat. Also provided herein are further multiplexed hgRNAs comprising additional direct repeats and spacers as well as methods of making and using thereof. Libraries comprising said hgRNAs or components thereof, cells, kits and reagents employed in the making or use thereof are also provided.

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 single stranded extension (in most embodiments, the single stranded extension comprises at least one modified nucleotide and/or phosphate back bone modification). Such single stranded extended Dicer-substrate siRNAs (DsiRNAs) were demonstrated to be effective RNA inhibitory agents compared to corresponding double stranded DsiRNAs.

Embodiments of the disclosure include compositions and methods for generating RNA nanostructures, particularly in a cell. In particular embodiments, RNA subunits comprising at least one three-way junction and at least one kissing loop are configured such that multiple RNA subunits can polymerize into a specific structure. In particular embodiments, the RNA subunits are configured such that sequence of at least one kissing loop is complementary to sequence of another kissing loop, such as on another RNA subunit, and the summation of multiple RNA subunits having specific individual structures results in a combined polymerized structure of a defined shape. In specific embodiments, an RNA nanostructure generated from methods herein is utilized for an application, such as manufacturing or genetic modifications in a cell.

The present invention relates to a nucleic acid molecule simultaneously inhibiting the expression of mTOR gene and STAT3 gene, and an anticancer pharmaceutical composition comprising the same. More specifically, base-paired siRNA or shRNA of the present invention, designed to simultaneously inhibit the expression of cancer-related mTOR gene and STAT3 gene in order to surmount the problem that siRNA or shRNA does not achieve high therapeutic effects due to the target specificity thereof, has the effect of promoting the death of cancer cells. In addition, the nucleic acid has the effect of synergistically enhancing the apoptosis of cancer cells when used in combination with an anticancer agent, finding useful applications as an anticancer composition or anticancer aid against various carcinomas.

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 single stranded extension (in most embodiments, the single stranded extension comprises at least one modified nucleotide and/or phosphate back bone modification). Such single stranded extended Dicer-substrate siRNAs (DsiRNAs) were demonstrated to be effective RNA inhibitory agents compared to corresponding double stranded DsiRNAs.

Provided herein are processes for preparing an oligomer (e.g., a morpholino oligomer). The synthetic processes described herein may be advantageous to scaling up oligomer synthesis while maintaining overall yield and purity of a synthesized oligomer.

A hyperbranched polymer includes a hyperbranched, hydrophobic molecular core, respective low molecular weight polyethyleneimine chains attached to at least three branches of the hyperbranched, hydrophobic molecular core, and respective polyethylene glycol chains attached to at least two other branches of the hyperbranched, hydrophobic molecular core. Examples of the hyperbranched polymer may be used to form hyperbranched polyplexes, and may be included in DNA or RNA delivery systems.

Provided herein are methods and compositions for long term treatment of spinal pain. In particular, use of double-stranded oligonucleotide decoys capable of binding to the DNA binding sites of two transcription factors are provided for treatment of spinal pain for over seven days, where the decoys are administered without a drug delivery system.

The present application relates to the field of RNA interference, more particularly RNA interference as applied in immunotherapy, such as adoptive cell therapy (ACT). Here, multiple shRNAs, designed to downregulate multiple targets are proposed. Also proposed are polynucleotides, vectors encoding the shRNA and cells expressing such shRNAs, alone or in combination with a protein of interest such as a chimeric antigen receptor (CAR) or T cell receptor (TCR). These cells are particularly suitable for use in immunotherapy.