Provided herein are compositions, systems, kits, and methods for treating a subject, and/or a subject's pre-adipocytes and/or adipocytes, with a composition containing a nucleic acid sequence encoding a protein or other biologically active nucleic acid-encoded molecule (BANEM), or a vector containing the nucleic acid sequence, wherein the treating comprises: a) injecting the composition into one or more subcutaneous (SC) regions of the subject such that one or more protein, or other BANEM, is detectable in a blood, serum, or plasma sample from the subject; and/or b) injecting the composition into one or more SC regions of the subject such that in-vivo transfected pre-adipocytes and/or adipocytes (e.g., transfected cells of fat cell origin) are generated; and/or c) performing the following: i) contacting pre-adipocytes and/or adipocytes (e.g., cells of fat cell origin) from the subject ex-vivo with the composition such that ex-vivo transfected pre-adipocytes and/or adipocytes are generated, and ii) injecting the ex-vivo transfected pre-adipocytes and/or adipocytes into one or more SC regions of the subject.

The invention provides adeno-associated virus (AAV) Factor VIII (FVIII)-encoding/expressing vectors and virus, including AAV FVIII vectors with high expression activity and AAV FVIII vectors that express full-length or truncated functional FVIII protein. The invention also relates to methods of making the herein described AAV FVIII vectors, recombinant AAV FVIII virus particles comprising or expressing such vectors, associated pharmaceutical formulations comprising the same and therapeutic uses thereof.

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.

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).

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.

Provided is the use of as SUMF2 gene therapy target for preventing and/or treating an allergic asthma attack and reducing airway hyperresponsiveness. It is verified that the abnormal metabolic pathway of SUMF1/GAG causes epithelial cells to produce a similar immune memory and the epithelial cells can promote T.sub.H2 response when exposed to allergens again. In the present disclosure, SUMF2 gene in airway epithelial cells from a mouse is overexpressed using the adeno-associated virus vector 20 days before the induction of asthma. Compared with a control group, the present disclosure can significantly improve the lung airway inflammation in an asthmatic mouse. Therefore, the overexpression of SUMF2 can be used as a gene therapy target to prevent allergic asthma and reduce airway hyperresponsiveness. Therefore, the use of an adeno-associated virus to overexpress SUMF2 for the prevention of allergic asthma has broad use values and market prospects.

Provided herein, in some embodiments, are materials and methods for treating hemophilia A in a subject ex vivo or in vivo. Also provided herein, in some embodiments, are materials and methods for knocking in a coding sequence encoding a synthetic FVIII having a B domain substitute into a genome.

Provided herein are novel methods for delivering recombinant adeno-associated viral (rAAV) particles to the central nervous system of a mammal (e.g., a human). In aspects, the methods involve administering rAAV particles containing a heterologous nucleic acid to the striatum and causing expression of the heterologous nucleic acid in at least the cerebral cortex and the striatum of the mammal.

Provided herein are compositions that include one or more adeno-associated virus (AAVs) vectors and methods of inducing differentiation of a hair cell using these vector(s).

The present invention features a dual vector system for disrupting and replacing a target gene comprising a mutation (e.g., dominant, recessive mutation). Embodiments of the invention may also provide compositions comprising the dual vector system, and methods of using the dual vector system, including but not limited to methods of modifying the genome of a cell, methods of genomic editing, and methods of treating cells or a subject suffering from a genetic disease comprising a mutation.