A method of treating an osmidrosis condition in a subject can include administering a therapeutic agent in an amount that is effective to inhibit expression of an ABCC11 gene in a target cell of the subject to an osmidrosis-reducing level. A therapeutic composition for treating an osmidrosis condition in a subject can include a therapeutically effective amount of an ABCC11 gene-inhibiting agent and a pharmaceutically acceptable carrier.

Provided are peptide nucleic acid derivatives targeting a part of the human HIF-1α pre-mRNA. The peptide nucleic acid derivatives potently induce exon skipping to yield splice variants of HIF-1α mRNA in cells, and are useful to treat indications or conditions involving the overexpression of HIF-1α.

A method to treat diseases or conditions associated with the human MMP-1 gene transcription involving administration of the peptide nucleic acid derivative according to claim 1 to a subject. The present invention provides the peptide nucleic acid derivative according to claim 1 which targets 5′ splice site of the human MMP-1 pre-mRNA “exon 5”. The peptide nucleic acid derivatives in the present invention strongly induce splice variants of the human MMP-1 mRNA in cell and are very useful to treat conditions or diseases of skin aging associated with the human MMP-1 protein.

Chemical syntheses of guide molecules are disclosed, along with compositions and methods relating thereto. A cost-effective and straightforward chemical synthesis of high-purity unimolecular guide molecules with minimal n−1 and/or n+1 species, truncation species, and other contaminants by providing, among other things, methods for synthesizing unimolecular guide molecules that involve cross-linking two or more pre-annealed guide fragments.

The invention provides an oligonucleotide comprising an inosine, and/or a nucleotide containing a base able to form a wobble base pair or a functional equivalent thereof, wherein the oligonucleotide, or a functional equivalent thereof, comprises a sequence which is complementary to at least part of a dystrophin pre-m RNA exon or at least part of a non-exon region of a dystrophin pre-m RNA said part being a contiguous stretch comprising at least 8 nucleotides. The invention further provides the use of said oligonucleotide for preventing or treating DMD or BMD.

The present invention relates to oligonucleotide inhibitors of the TSC22D4 activity or expression and their uses for the prevention, treatment, and/or regulation of insulin resistance, metabolic syndrome and/or diabetes and/or for improving insulin sensitivity in a mammal.

The present invention provides gapped oligomeric compounds comprising from 1 to about 3 internucleoside linkages having one of formulas I to XVI. In certain embodiments, inclusion of from 1 to about 3 internucleoside linkages of one of formulas I to XVI, improves selectivity for a target RNA relative to an off target RNA. In certain embodiments, the improved selectivity also provides an improved toxicity profile. Certain such oligomeric compounds are useful for hybridizing to a complementary nucleic acid, including but not limited, to nucleic acids in a cell. In certain embodiments, hybridization results in modulation of the amount of activity or expression of the target nucleic acid in a cell.

Provided are compounds, methods, and pharmaceutical compositions for increasing the amount or activity of STMN2 RNA in a cell or animal, and in certain embodiments increasing the amount of STMN2 protein in a cell or animal. Such compounds, methods, and pharmaceutical compositions are useful to ameliorate at least one symptom of a neurodegenerative disease. Such symptoms include ataxia, neuropathy, synaptic dysfunction, deficits in cognition, and decreased longevity. Such neurodegenerative diseases include amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), Alzheimer's disease (AD), and dementia with Lewy bodies (DLB).

In an embodiment, a strand displacement system including a DNA/PNA complex, an input DNA strand, where the DNA/PNA complex binds to the input DNA strand forming a complex and displaces a PNA intermediate and forms an activated domain on the PNA, and a Bi complex that reacts with the activated domain on the PNA to thereby release an output DNA strand. In an additional embodiment, a fluorogenic sensor including a heteroduplex between an achiral PNA strand and a fluorogenic aptamer, where the fluorogenic aptamer includes L-RNA, an input DNA strand, where the input DNA strand binds to the heteroduplex and displaces an incumbent fluorogenic aptamer strand and forms an activated domain on that strand, and a dye.

A composition according to an embodiment of the present invention includes nucleic acid molecules which are capable of effectively inhibiting the expression level of connective tissue growth factor (CTGF) and collagen by RNA interference (RNAi), thereby preventing or treating a variety of fibroproliferative diseases due to overexpression of CTGF or collagen.