The invention relates to improvements in drug delivery and more particularly to the use of Cell Penetrating Agents (CPA's) or Cell Penetrating Peptides (CPP's) which have been stabilized by, for example: i) stapling two amino acids to form Stapled CPP's (StaP's) or ii) stitching three or more amino acids to form stitched CPP's (StiP's). These stabilized CPP's are conjugated to a drug or Biologically Active Compound (BAC) directly or via a Bi-Functional Linker (BFL) so that the BAC can be carried through a cell membrane by the CPP. The resulting molecules are referred to as Drug Carrying Cell Penetrating Molecules (DCCPM's). The preferred BAC is an electrically low charge carrying oligonucleotide such as a phosphorodiamidate morpholino oligonucleotide (PMO). The invention also relates to a method of facilitating the uptake of a BAC into a cell, the use of a DCCPM in the treatment of a disease requiring alteration of an endogenous or exogenous gene, a method of improving the bioavailability of a drug or BAC, a method of introducing a drug or BAC to a site which is refractory to the drug or BAC in its native state, a method of treating a subject comprising administering the DCCPM's of the invention and to a pharmaceutical composition comprising the DCCPM and one or more pharmaceutically acceptable excipients.

The present invention relates to an RNA encoding a therapeutic protein, in particular a collagenase, growth factor, cytokine, receptor, chaperone or signal transduction inhibitor. In particular, the present invention relates to RNA suitable for treatment of wounds, specifically for promoting wound healing. The present invention concerns such RNA as well as pharmaceutical compositions and kits and combinations comprising the RNA. Furthermore, the present invention relates to the RNA, pharmaceutical compositions, kits as disclosed herein for use in the treatment of wounds, specifically for promoting wound healing.

The present invention relates to vectors and compositions for the treatment of glycogen storage disease III.

The present invention provides compositions, systems, kits, and methods for expression of one or more biomolecules in a subject, human or non-human mammal, (e.g., at therapeutic levels for the extended periods of time required to produce therapeutic effects). In certain embodiments, compositions, systems, kits, and methods are provided that comprise a first composition comprising polycationic structures (e.g., empty cationic liposomes, cationic micelles, cationic emulsions, or cationic polymers) and a second composition comprising expression vectors (e.g., non-viral expression vectors not associated with liposomes or other carriers) encoding one or more biomolecules of interest.

Editing of VEGFR2 abrogated angiogenesis in two mouse models of oxygen-induced retinopathy (OIR) and laser-induced choroid neovascularization (CNV). Provided are compositions, e.g., Adeno-Associated Virus (AAV) Vectors comprising sequences encoding CRISPR/Cas9 proteins and guide RNA, and methods of use thereof for editing of Vascular endothelial growth factor receptor 2 (VEGFR2) gene to treat ocular disease associated with pathological angiogenesis, e.g., neovascular age-related macular degeneration (AMD), proliferative diabetic retinopathy (PDR) and retinopathy of prematurity (ROP).

Provided herein are spirolactone compounds of Formula I that are useful as inhibitors of ACC1 and/or ACC2. The spirolactone compounds described herein can be used for treating a disease or disorder associated with aberrant ACC1 and/or ACC2 activities, for example, non-alcoholic steatohepatitis (NASH), acne, obesity, diabetes, and cancer. Also provided herein are pharmaceutical compositions comprising the spirolactone compound of Formula I, or pharmaceutically acceptable salt thereof. ##STR00001##

The present disclosure provides recombinant nucleic acids comprising one or more polynucleotides encoding a Serine Protease Inhibitor Kazal-type (SPINK) polypeptide (e.g., a SPINK5 polypeptide); viruses comprising the recombinant nucleic acids; compositions and formulations comprising the recombinant nucleic acids and/or viruses; methods of their use (e.g., for the treatment of Netherton Syndrome); and articles of manufacture or kits thereof.

The present invention relates to a method of trans-activating a homologous gene of at least one gene of interest and optionally deactivation of at least one gene of interest, wherein the mRNA encoded by the at least one gene of interest comprises a mutation compared to a control, and wherein the method comprises the steps as described in the present application. The present invention further relates to an in vitro method of diagnosing a disease, wherein the method comprises the steps of: a) Inducing the expression of the mRNA encoded by at least one gene of interest in a cell or tissue sample obtained from a subject; b) isolating the mRNA of step a); c) analyzing the sequence of the isolated mRNA of step b) and d) thereby detecting a mutation of the mRNA compared to a control, which is indicative for the presence of the disease.

Provided herein, in some embodiments, are nucleic acid constructs encoding RNA molecules comprising one or more introns that can be regulated (e.g., autoregulated), and that are useful for delivery in a recombinant viral vector. Aspects of the application provide compositions and methods for delivering regulated (e.g., auto-regulated) gem expression constructs to a subject.

The present invention relates to a composition which is for preventing or treating bone diseases and includes CCR2 as an active ingredient. It was confirmed that a C—C chemokine receptor type 2 (CCR2) protein, a polynucleotide encoding the CCR2 protein, or a mesenchymal stem cell transduced with the CCR2 according to the present invention neutralize bone disease factor MCP-1, thereby reducing the collagen epitope (CTX-II) and collagen metabolism factors (MMP1 and MMP3) relating to collagen absorption in the body. In addition, it was confirmed that the expression of the SOX9 gene and anti-inflammatory cytokines (TGF-β and IL-10) related to cartilage differentiation was significantly increased. Thus, the present invention has excellent regenerative ability against osteoarthritis and excellent pain suppression and alleviation effects, and thus can be effectively used for preventing or treating bone diseases such as osteoarthritis.