The invention relates to the control of gene expression. Specifically, the invention provides compositions and methods for the production and use of recombinant nucleic acid molecules that have the ability to specifically downregulate an expressed target gene in vivo. In some aspects, the invention provides methods for producing a hairpin DNA molecule where part of the molecule is derived from an mRNA that is a target for a small interfering RNA (siRNA) derived from the hairpin. In other aspects, the invention provides synthetic hairpin adapter oligonucleotides that are used in the construction of siRNA-producing cassettes. In other aspects, the invention provides methods for testing for the presence or absence of specific inhibitory activity of an RNAi trigger molecule, and in still other aspects, the invention provides methods for identifying an active RNAi trigger molecule from a library of RNAi trigger molecules. In still other aspects, the invention provides methods for identifying a polynucleotide from a plurality of candidate target polynucleotides that is specifically targeted by an RNAi trigger molecule. In other aspects, the invention provides epi-allelic series of hypomorphic RNAi trigger molecules specific for any gene of interest, where the series of RNAi trigger molecules have a variety of uses including analysis of gene function and drug target development.

Molecular target for healing or treating wounds and, in particular chronic, human wounds, are described. The molecular target is PTPRK, or a protein 50% homologous therewith, and which retains the same activity as PTPRK protein. Further, methods and novel therapeutics are described for treating said wounds.

Provided is a drug that allows highly-efficient skipping of exon. The present invention provides an antisense oligomer wherein two or more unit oligomers targeting sequences that are neither consecutive nor overlap with each other in the same exon are connected.

The oligonucleotide compositions of the present invention make use of combinations of oligonucleotides. In one aspect, the invention features an oligonucleotide composition including at least 2 different oligonucleotides targeted to a target gene. This invention also provides methods of inhibiting protein synthesis in a cell and methods of identifying oligonucleotide compositions that inhibit synthesis of a protein in a cell.

The present invention relates to chirally controlled oligonucleotides, chirally controlled oligonucleotide compositions, and the method of making and using the same. The invention specifically encompasses the identification of the source of certain problems with prior methodologies for preparing chiral oligonucleotides, including problems that prohibit preparation of fully chirally controlled compositions, particularly compositions comprising a plurality of oligonucleotide types. In some embodiments, the present invention provides chirally controlled oligonucleotide compositions. In some embodiments, the present invention provides methods of making chirally controlled oligonucleotides and chirally controlled oligonucleotide compositions.

The present disclosure generally relates to compositions and methods for the genetic modification of cells. In particular, the disclosure relates to CRISPR reagents and the use of such reagents.

The present invention concerns methods and reagents useful in modulating gene expression in a variety of applications, including use in therapeutic, diagnostic, target validation, and genomic discovery applications. Specifically, the invention relates to synthetic chemically modified small nucleic acid molecules, such as short interfering nucleic acid (siNA), short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (miRNA), and short hairpin RNA (shRNA) molecules capable of mediating RNA interference (RNAi) against target nucleic acid sequences. The small nucleic acid molecules are useful in the treatment of any disease or condition that responds to modulation of gene expression or activity in a cell, tissue, or organism.

The present invention is directed to modified oligonucleotides having the following Formula (I) ##STR00001##
wherein one or more of phosphate groups are substituted at phosphorus, and methods for their synthesis. The modified oligonucleotides are useful for diagnostic applications involving sequence specific recognition of a nucleic acid and for use in a method of medical treatment.

Provided is a drug that allows highly-efficient skipping of exon. The present invention provides an antisense oligomer wherein two or more unit oligomers targeting sequences that are neither consecutive nor overlap with each other in the same exon are connected.

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).