The present invention relates to transcription regulatory elements (TREs) such as promoters, which may be used to express a transgene within a cell such as a mammalian cell. The invention further relates to polynucleotides and vectors comprising such transcription regulatory elements, which may be operably linked to a transgene, as well as methods of gene therapy based on using such vectors.

Methods and compositions for producing heme and treating sideroblastic anemia are disclosed.

The present disclosure relates to compositions and methods useful for treating glycogen storage disorders, such as type II glycogen storage disorder, also referred to herein as Pompe disease. Using the compositions and methods of the disclosure, a patient (e.g., a mammalian patient, such as a human patient) having Pompe disease may be administered a viral vector, such as an adeno-associated viral (AAV) vector, that contains a transgene encoding acid alpha-glucosidase.

The present invention includes compositions and methods comprising viral vector systems for multiplexed activation of endogenous genes as immunotherapy and viral-based immune-gene therapy.

The present disclosure relates to AAV gene therapy vectors, AAV replicons, and pharmaceutical compositions for delivering a human HDAC8 gene to a subject for treating Cornelia de Lange Syndrome. In addition, methods of treatment and gene transfer are provided.

Methods for introducing a gene into a cell of the inner ear, e.g., a cochlear or vestibular cell, e.g., a hair cell, e.g., for therapy, that include the use of exosomes associated with one or more adeno-associated viral (AAV) particles.

The present invention relates to the field of recombinant viral vectors suitable for the delivery of therapeutic genes in vivo. Described is an adeno-associated virus (AAV) vector comprising (i) a human growth hormone intron 3 (hGHi3) sequence (ii) a synapsin promoter sequence and/or (iii) a progranulin 3′ untranslated region (UTR) sequence, operably coupled to a polynucleotide sequence encoding a polypeptide of interest. Specific use of such a vector lies in the enhanced expression of a polypeptide of interest, such as progranulin (PGRN), to treat subjects who have a genetic mutation or intrinsic polypeptide level that is below a physiologically normal level.

The present invention relates to treatment of AR-related disorders by modulating the levels of AR2, which is a naturally occurring AR variant and is capable of modulating AR transcriptional activity.

Provided are recombinant nucleic acids (e.g., vectors), and related methods, for expression of a target gene in a host cell. The recombinant nucleic acids comprise a promoter comprising a nucleic acid sequence having at least 70% sequence identity to a sequence selected from SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8 and SEQ ID NO: 9; a cloning site for insertion of a nucleic acid encoding the target gene; and at least one non-promoter regulatory element required for the expression of the target gene in the host cell.

The present disclosure features methods and compositions for treating Alzheimer's disease. The disclosed methods comprise administering to a subject having or suspected of having Alzheimer's a hematopoietic stem progenitor cell expressing at least one neuroprotective agent, such as ApoE2, Trem2, and/or a metallothionein.