A recombinant adeno-associated virus (rAAV) comprising an AAV capsid and a vector genome comprising a frataxin gene is provided. Also provided is a composition containing an effective amount of rAAV to ameliorate symptoms of Freidreich’s ataxia, including, e.g., reduction in progression towards neurocognitive decline and/or cardiomyopathy.

The present disclosure provides expression constructs designed to provide for expression of therapeutic proteins from engineered cells. The engineered cells may be encapsulated into implantable elements that allow for the therapeutic protein to be released into from the capsule while protecting the cell from the immune system of a patient into which the capsule is implanted.

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 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.

The present invention pertains to an inventive release mechanism for extracellular vesicle (EV)-mediated intracellular and intramembrane delivery of therapeutic polypeptides. More specifically, the invention relates to EVs comprising polypeptide constructs which comprise a therapeutic polypeptide releasably attached to an exosomal polypeptide. Furthermore, the present invention pertains to manufacturing methods, pharmaceutical compositions, medical uses and applications, and various other embodiments related to the inventive EVs.

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.

The present invention is related to compositions and methods for gene therapy. Several approaches described herein utilize the Neisseria meningitidis Cas9 system that provides a hyperaccurate CRISPR gene editing platform. Furthermore, the invention incorporates full length and truncated single guide RNA sequences that permit a complete sgRNA-Nme1Cas9 vector to be inserted into an adeno-associated viral plasmid that is compatible for in vivo administration. Furthermore, Type II-C Cas9 orthologs have been identified that target protospacer adjacent motif sequences limited to between one-four required nucleotides.

The present disclosure provides ghost nanovesicles (gNVs) that are deficient in cytosolic components. Methods of making such vesicles and therapeutic uses of such vesicles are also provided. The gNVs may be used in preventing or treating conditions that may benefit from administration of the gNVs. Such conditions include conditions that involve inflammation.

Disclosed herein are methods for modulating hair growth and increasing hair follicle stem cell activation in an individual in need thereof. This includes administering an agent that modulates a Gas6-Tyro3-Axl-Mertk (TAM) interaction or pathway.

Provided are variant adeno-associated virus (AAV) capsid proteins and recombinant AAV virions having one or more variant AAV capsid proteins. Also provided are compositions and methods for the use of the recombinant AAV virions, such as for the treatment or prophylaxis of a disease or disorder.