The present invention relates to PIKFYVE antisense oligonucleotides (ASOs), pharmaceutical compositions containing them, and methods for treating, inhibiting, suppressing, and preventing neurological diseases with them.

Compositions and methods are provided for the silencing of the NSD3 gene. Specifically, siRNA compositions are provided that contain siRNA molecules that target the wild-type NSD3 gene or the NSD3.sub.T1232A mutant. Methods for using these compositions for treating cancer also are provided.

Provided herein, inter alia, are double stranded oligonucleotide molecules and methods of making the molecules. The double stranded oligonucleotide molecules include a first oligonucleotide strand comprising a first nucleic acid sequence bound to a second nucleic acid sequence through a first spacer, wherein said second nucleic acid sequence is bound to a third nucleic acid sequence through a second spacer and a second oligonucleotide strand comprising a fourth nucleic acid sequence bound to a fifth nucleic acid sequence through a third spacer, wherein said fifth nucleic acid sequence is bound to a sixth nucleic acid sequence through a fourth spacer, wherein the second nucleic acid sequence and the fifth nucleic acid sequence are hybridized to form a double stranded nucleic acid core of said double stranded oligonucleotide.

The invention provides gene therapy vectors, such as adeno-associated vims (AAV) vectors, expressing a miniaturized human micro-dystrophin gene and method of using these vectors to express micro-dystrophin in skeletal muscle including diaphragm and cardiac muscle and to protect muscle fibers from injury, increase muscle strength and reduce and/or prevent fibrosis in subjects suffering from muscular dystrophy.

Described are improved linking agents that are useful for facilitating the attachment of targeting groups, pharmacokinetic (PK) enhancers or modifiers, or other delivery agents to oligonucleotides. The described linking agents may exhibit improved reaction yields, stability, and biological activity, particularly when used in connection with oligonucleotide-based compounds, such as RNA interference (RNAi) agents.

Disclosed herein are CpG conjugated nanoparticles for immunotherapy and photothermal therapy. The composition comprises class B CpG conjugated nanoparticles and/or a class C CpG conjugated nanoparticles where the class B CpG conjugated nanoparticles comprises a nanoparticle core and a class B CpG conjugated thereto and the class C CpG conjugated nanoparticles comprises a nanoparticle core and a class C CpG conjugated thereto.

The present invention provides refillable drug delivery systems, as well as methods of refilling the systems, and methods of using them to treat diseases.

This application relates to therapeutic siRNA agents and methods of making and using the agents.

The present invention relates to compounds, compositions, and methods for the study, diagnosis, and treatment of traits, diseases and conditions that respond to the modulation of gene expression and/or activity, and/or modulate a gene expression pathway. Specifically, the invention relates to double-stranded nucleic acid molecules including small nucleic acid molecules, such as short interfering nucleic acid (siNA) molecules that are capable of mediating or that mediate RNA interference (RNAi) against target gene expression.

Embodiments of the invention include drug delivery coatings and devices including the same. In an embodiment, the invention includes a drug delivery coating including a polymeric layer. The polymeric layer can include a hydrophilic outer surface. The coating can also include a matrix contacting the hydrophilic outer surface. The matrix can include a particulate hydrophobic therapeutic agent and a cationic agent. The polymeric layer can further include a hydrophilic polymer having pendent photoreactive groups and a photo-crosslinker including two aryl ketone functionalities. Other embodiments are also included herein.