In some aspects, the disclosure relates to compositions and methods of engineering a transgene. In some embodiments, the disclosure provides self-regulating recombinant nucleic acids, viral vectors and pharmaceutical compositions comprising a MeCP2 transgene. In some embodiments, compositions and methods described by the disclosure are useful for treating diseases and disorders associated with a loss of function mutation, for example Rett syndrome.

Hoxb5 identifies long-term hematopoietic stem cells. Expression of Hoxb5 distinguishes between LT-HSCs and non-LT-HSCs, and the marker identifies substantially all LT-HSC in the bone marrow. By utilizing fluorescent proteins under the endogenous expression control of Hoxb5, LT-HSC can be monitored and isolated, including without limitation detection and monitoring of HSC in bone morrow; production of LT-HSC from pluripotent stem cells such as iPS cells; for analysis of early stage LT-HSC; in screening methods for expansion and manipulation of LT-HSC, and the like.

The present invention includes compositions and methods for treating diseases or disorders associated with pathological calcification or pathological ossification. In certain embodiments, the diseases or disorders are selected from the group consisting of Generalized Arterial Calcification of Infancy (GACI), Idiopathic Infantile Arterial Calcification (IIAC), Ossification of the Posterior Longitudinal Ligament (OPLL), hypophosphatemic rickets, osteoarthritis, calcification of atherosclerotic plaques, PXE, hereditary and non-hereditary forms of osteoarthritis, ankylosing spondylitis, hardening of the arteries occurring with aging, calciphylaxis resulting from end stage renal disease and progeria.

The present disclosure provides, among other aspects, codon-altered polynucleotides encoding Factor VIII variants for expression in mammalian cells. In some embodiments, the disclosure also provides mammalian gene therapy vectors and methods for treating hemophilia A.

The present invention relates to regulatable adeno-associated virus (AAV) vectors as well as to their use in gene therapy. It further relates to corresponding nucleic acid molecules, host cells, non-human transgenic animals, pharmaceutical compositions and kits.

The present disclosure provides, among other aspects, codon-altered polynucleotides encoding Factor VIII variants for expression in mammalian cells. In some embodiments, the disclosure also provides mammalian gene therapy vectors and methods for treating hemophilia A.

This document provides methods and materials for generating GABAergic neurons in brains. For example, methods and materials for using nucleic acid encoding a NeuroD1 polypeptide and nucleic acid encoding a Dlx2 polypeptide to trigger glial cells (e.g., NG2 glial cells or astrocytes) within the brain (e.g., striatum) into forming GABAergic neurons (e.g., neurons resembling medium spiny neurons such as DARPP32-positive GABAergic neurons) that are functionally integrated into the brain of a living mammal (e.g., a human) are provided.

The disclosure relates to compositions and methods for rAAV-mediated delivery of a transgene to a subject. In some embodiments, the rAAV transduces the prostate tissue of a subject. In some embodiments, the methods are useful for treatment of prostate disease (e.g., prostatitis, BPH, prostate cancer).

Factor VIII variants and methods of use thereof are disclosed. In particular embodiments, Factor VIII variants are expressed more efficiently by cells over wild-type Factor VIII proteins, are secreted at increased levels by cells over wild-type Factor VIII proteins, exhibit enhanced activity over wild-type Factor VIII proteins and are packaged more efficiently into viral vectors.

The present disclosure provides, among other aspects, codon-altered polynucleotides encoding Factor VIII variants for expression in mammalian cells. In some embodiments, the disclosure also provides mammalian gene therapy vectors and methods for treating hemophilia A.