The present invention relates to a nucleic acid complex having a novel structure, which may introduce a bioactive nucleic acid into cells, a composition for treating or diagnosing disease comprising the same, and a method of regulating target gene expression using the same, and more particularly to a nucleic acid complex in which a bioactive nucleic acid, which comprises a material for facilitating endosomal escape, and a carrier peptide nucleic acid, are complementarily bound to each other, a composition for treating or diagnosing disease comprising the same, a composition for regulating target gene expression using the same, and a method of regulating target gene expression using the same.

A nucleic acid complex of Structural Formula (1) according to the present invention, which comprises a bioactive nucleic acid and a carrier peptide nucleic acid, may increase the stability of the bioactive nucleic acid, reduce loss of the bioactive nucleic acid, such as precipitation caused by self-aggregation, increase the intracellular delivery efficiency of the bioactive nucleic acid, and easily regulate target gene expression.

Disclosed herein are systems, methods, and compositions for rapidly and reversibly destabilizing a target protein in vitro or in vivo, in the presence or absence of a cell-permeable, synthetic molecule or ligand.

Disclosed herein are systems, methods, and compositions for rapidly and reversibly destabilizing a target protein in vitro or in vivo, in the presence or absence of a cell-permeable, synthetic molecule or ligand.

The present invention relates to the discovery of a novel molecular pathway involved in long-term hyperexcitability of sensory neurons, which, in higher animals, is associated with persistent pain. It is based on the discovery that, following injury to an axon of a neuron, an increase in nitric oxide synthase activity results in increased nitric oxide production, which, in turn, activates guanylyl cyclase, thereby increasing levels of cGMP. Increased cGMP results in activation of protein kinase G (PKG), which then is retrogradely transported along the axon to the neuron cell body, where it phosphorylates MAPKerk.

A modulator of PDE1A and/or PDE1C can be used as a medicament, in particular in the prevention or treatment of synucleinopathies, such as multiple system atrophy, dementia with Lewy bodies, Parkinson's disease, pure autonomic failure, rapid eye movement sleep behavior disorder, inherited synucleinopathies caused by mutations or multiplications of the SNCA gene, or synucleinopathies caused by mutations in other genes including, but not limited to, GBA, LRRK2 and PARK2.

Disclosed herein are systems, methods, and compositions for rapidly and reversibly destabilizing a target protein in vitro or in vivo, in the presence or absence of a cell-permeable, synthetic molecule or ligand.

The invention provides a polypeptide possessing anti-hypertrophic activity in a cardiac myocyte, wherein the polypeptide is a mutant variant derived from wild-type PDE3A1 protein and wherein the wild-type PDE3A1 protein has the amino acid sequence given in SEQ ID NO:1 at amino acid position 146 to 1141.

The present invention relates to RNAi agents, e.g., double stranded RNA (dsRNA) agents, targeting a metabolic disorder-associated target gene, e.g., inhibin subunit beta E (INHBE), activin A receptor type 1C (ACVR1C), perilipin-1 (PLIN1), phosphodiesterase 3B (PDE3B), or inhibin subunit beta C (INHBC) gene. The invention also relates to methods of using such RNAi agents to inhibit expression of a metabolic disorder-associated target gene and to methods of preventing and treating a metabolic disorder, e.g., metabolic syndrome.

The present disclosure provides methods of treating a subject having a liver disease or type 2 diabetes, and methods of identifying subjects having an increased risk of developing a liver disease or type 2 diabetes.

The invention provides a polypeptide possessing anti-hypertrophic activity in a cardiac myocyte, wherein the polypeptide is a mutant variant derived from wild-type PDE3A1 protein and wherein the wild-type PDE3A1 protein has the amino acid sequence given in SEQ ID NO:1 at amino acid position 146 to 1141.