The present invention relates to an RNA suitable for treatment or prophylaxis of liver diseases. In particular, the present invention provides an RNA encoding at least one peptide or protein selected from the group consisting of an extracellular matrix protease, CCAAT/enhancer-binding protein alpha (CEBPA), TNF-related apoptosis-inducing ligand (TRAIL), Hepatocyte Growth Factor (HGF), hepatocyte nuclear factor 4 alpha (HNF4A), fibroblast growth factor 21 (FGF21), opioid growth factor receptor-like 1 (OGFRL1), Relaxin 1 (RLN1), Relaxin 2 (RLN2) and Relaxin 3 (RLN3), or a fragment or a variant of any of these peptides or proteins. The present invention concerns said RNA as well as compositions and kits comprising the RNA. Furthermore, the present invention relates to the RNA, compositions or kits as disclosed herein for use as a medicament, in particular for treatment or prophylaxis of a liver disease. The present invention also provides the use of the RNA, compositions or kits as disclosed herein for increasing the expression of said encoded protein, in particular in gene therapy.

The present invention relates to RNAi agents, e.g., double stranded RNA (dsRNA) agents, targeting the transthyretin (TTR) gene. The invention also relates to methods of using such RNAi agents to inhibit expression of an TTR gene and to methods of preventing and treating an TTR-associated disorder, e.g., senile systemic amyloidosis (SSA), systemic familial amyloidosis, familial amyloidotic polyneuropathy (FAP), familial amyloidotic cardiomyopathy (FAC), leptomeningeal/Central Nervous System (CNS) amyloidosis, and hyperthyroxinemia.

This invention generally relates to a composition and its method of use for inducing adult stem cell (ASC) expansion and/or derivation in vitro, using miR-302-like pre-miRNAs, shRNAs and/or siRNAs, all of which contain a shared sequence of 5′-UAAGUGCUUC CAUGUUU-3′ (SEQ ID NO: 7) in the 5′-end, and further in conjunction with the use of some wound-healing-related defined factors, including but not limited to basic fibroblast growth factor (bFGF)/fibroblast growth factor 2 (FGF-2), leukemia inhibitory factor (LIF), insulin-like growth factor (IGF), Epidermal growth factor (EGF), platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), transforming growth factor (TGF), tumor necrosis factor (TNF), stem cell factor (SCF), homeobox proteins (HOX), Notch, GSK, Wnt/beta-Catenin signals, interleukins, and/or bone morphogenetic proteins (BMPs). The principle of the present invention is related to a novel mechanism of inducible symmetric ASC division recently found in a skin wound healing model in vivo. The resulting amplified ASCs are useful for treating a variety of human aging- and cell dysfunction-associated disorders, including but not limited to Alzheimer's disease, Parkinson's disease, motor neuron disease, stroke, diabetes, osteoporosis, myocardial infraction, hemophilia, anemia, AIDS, leukemia, lymphoma and many kinds of cancers as well as aging.

Compositions and methods are provided for reprogramming dermal fibroblasts to exhibit vasculogenic properties including the ability to stimulate vasculogenesis in vivo. In accordance with one embodiment such compositions are used in conjunction with standard treatment for use on chronic wounds including in diabetic patients.

Provided are a nucleic acid with improved ability to inhibit the expression of the MEX3B gene with low occurrence of cytotoxicity side effects, an MEX3B gene expression inhibiting agent that includes the nucleic acid, a method for inhibiting MEX3B gene expression, and a prophylactic or therapeutic drug for a disease caused by MEX3B gene expression. The present invention is a nucleic acid that is any of (1) to (3): (1) an oligonucleotide that comprises the nucleotide sequence represented by SEQ ID NO: 1 or 2; (2) an antisense oligonucleotide that inhibits expression of the MEX3B gene and that comprises a nucleotide sequence derived by deletion, substitution, and/or addition of one or two nucleotides in the nucleotide sequence represented by SEQ ID NO: 1 or 2; and (3) an antisense oligonucleotide that inhibits expression of the MEX3B gene and that includes the nucleotide sequence represented by SEQ ID NO: 3.

Compositions and methods for treating a subject are provided. The compositions may include a short interfering RNA (siRNA) molecule comprising a sense RNA strand and an anti-sense RNA strand, the sense and anti-sense RNA strands forming an RNA duplex. The method may include administering a medical composition including an agent to the subject, wherein the agent is configured to reduce uridine 5′-diphospho-glucuronosyltransferase (UGT) levels in the subject. The sense RNA strand or the anti-sense RNA strand may be 15 to 25 nucleotides in length. The sense RNA strand and the anti-sense RNA strand may be 70%-100% complementary.

Enhanced, specific nucleic acid targeting complexes comprising endo and exonuclease activity, and related methods that allow both targeted degradation of specific and/or non-specific nucleic acids in vivo and specific temporal regulation of nuclease activity to prevent off-target activity are disclosed herein. Through practice of the disclosure, nucleic acids, and cells harboring them, such as cancer cells or pathogens, are selectively degraded in vivo.

This disclosure relates to compounds, compositions, and methods useful for reducing α-1 antitrypsin target RNA and protein levels via use of dsRNAs, e.g., Dicer substrate siRNA (DsiRNA) agents.

The present disclosure provides modified short-interfering ribosomal nucleic acid compositions that have one or more uracil bases replaced a 5-fluorouracil molecule. More specifically, the present disclosure reveals that the replacement of uracil nucleotides within an siRNA nucleotide sequence with a 5-fluorouracil increases the ability of the short interfering RNA to inhibit cancer progression and tumorigenesis when compared to known cancer therapeutics. As such, the present disclosure provides various short-interfering nucleic acid compositions having 5-fluorouracil molecules incorporated in their nucleic acid sequences and methods for using the same. The present disclosure further provides pharmaceutical compositions comprising the modified nucleic acid compositions, and methods for treating cancers using the same.

The invention provides methods for treating or preventing microbial (eg, bacterial) infections and means for performing these methods. In particular, treatment of infections requiring rapid and durable therapy is made possible, such as for treating acute conditions such as septicemia, sepsis, SIRS or septic shock. The invention is particularly useful, for example, for treatment of microbes such as for environmental, food and beverage use. The invention relates inter alia to methods of controlling microbiologically influenced corrosion (MIC) or biofouling of a substrate or fluid in an industrial or domestic system. The invention also useful for the treatment of pathogenic bacterial infections in subjects receiving a treatment for a disease or condition, such as a transplant or a treatment for cancer, a viral infection or an autoimmune disease.