The invention described herein provides gene therapy vectors, such as adeno-associated virus (AAV) vectors, that co-express a functional protein (such as a miniaturized human micro-dystrophin gene product) and one or more additional coding sequences for an RNAi sequence (siRNA, shRNA, miRNA), an antisense sequence, a guide sequence for a gene editing enzyme (such as an sgRNA for CRISPR/Cas9, or a crRNA for CRISPR/Casl2a), and/or a micro RNA, and methods of using the vectors to treat subjects suffering from a muscular dystrophy such as DMD/BMD.

A method is provided for generating RNA nanoparticles having modified nucleotides and/or having increased nuclease resistance where the RNA nanoparticles are formed cotranscriptionally by T7 RNA polymerase in the presence of manganese ions.

A ribozyme comprising a target-binding domain, a polynucleotide encoding the same, a kit comprising the same, and uses thereof.

A gene RNAi vector is constructed with a V-ATPase subunit E gene fragment, a COO2 gene fragment, or a combination of the V-ATPase subunit E gene fragment and the COO2 gene fragment, then transferred into a plant, and expressed in the plant to produce dsRNA of the V-ATPase subunit E gene, the COO2 gene, or the combination of the V-ATPase subunit E gene and the COO2 double gene, and therefore the aphid growth is suppressed, and the plant is enhanced in pest resistance.

The present disclosure provides compositions and methods for inhibiting herpesvirus replication in a cell infected with herpesvirus. The composition includes a double stranded DNA molecule including a sequence of a cis regulatory sequence (crs) of a herpesvirus, wherein the crs is flanked on the 5′ end by a first sequence of at least 2 base pairs and on the 3′ end by a second sequence of at least 2 base pairs.

The present document describes nucleic acid structures comprising a plurality of annealed motifs that are made from complementary oligonucleotides having domains with sequences complementary to other nucleotides of the motif. The annealed motifs may be anchored to surfaces, and functional elements may be attached to the annealed motifs. The nucleic acid structures may used to make sensors therefrom. The present document also describes methods to generate said nucleic acid structures.

Immunomodulating polynucleotides are disclosed. The immunomodulating polynucleotides may contain 5-modified uridine, 5-modified cytidine, a total of from 6 to 16 nucleotides, and/or one or more abasic spacers and/or internucleoside phosphotriesters. Also disclosed are conjugates containing a targeting moiety and one or more immunomodulating polynucleotides. The immunomodulating polynucleotides and conjugates may further contain one or more auxiliary moieties. Also disclosed are compositions containing the immunomodulating polynucleotides or the conjugates containing one or more stereochemically enriched internucleoside phosphorothioates. Further disclosed are pharmaceutical compositions containing the immunomodulating polynucleotides or the conjugates and methods of their use.

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.

The present invention relates to methods of administering to a subject multimeric oligonucleotides having monomeric subunits joined by linkers. The multimeric oligonucleotides have a molecular weight of at least about 45 kD and other characteristics, such that their clearance due to glomerular filtration is reduced. The present invention also relates to such multimeric oligonucleotides and methods of synthesizing such multimeric oligonucleotides.

The present invention provides a multi-targeting nucleic acid construct comprising at least: (a) a first nucleic acid portion that is at least partially complementary to at least a first portion of RNA transcribed from a target gene; (b) a second nucleic acid portion that is at least partially complementary to at least a second portion of RNA transcribed from a target gene, which target gene may be the same or different to the target gene defined in (a); (c) a third nucleic acid portion that is at least partially complementary to the first nucleic acid portion of (a), so as to form a first nucleic acid duplex region therewith; (d) a fourth nucleic acid portion that is at least partially complementary to said second nucleic acid portion of (b), so as to form a second nucleic acid duplex region therewith. The construct is designed so that subsequent to in vivo administration the construct disassembles to yield at least first and second discrete nucleic acid targeting molecules that respectively target RNA transcribed from the target genes of (a) and (b). Typically, the first nucleic acid targeting molecule is capable of modulating expression of the target gene of (a), and comprises, or is derived from, at least the first nucleic acid portion of (a). Typically, the second nucleic acid targeting molecule is capable of modulating expression of said target gene of (b), and comprises, or is derived from, the second nucleic acid portion of (b).