Artificial expression constructs for selectively modulating gene expression in selected central nervous system cell types are described. The artificial expression constructs can be used to selectively express synthetic genes or modify gene expression in astrocytes, oligodendrocytes, microglia, pericytes, SMC, or endothelial cells.

Provided herein are gene therapy methods for the treatment of mucopolysaccharidosis type IV A (MPS IV A) involving the use of recombinant adeno-associated viruses (rAAVs) to deliver human N-acetylgalactosamine-6-sulfate sulfatase (hGALNS) to the bone of a human subject diagnosed with MPS IVA. Also provided herein are rAAVs that can be used in the gene therapy methods and methods of making such rAAVs.

Disclosed are nucleic acid vectors comprising a CBh promoter operably linked to a heterologous sequence encoding a G-protein coupled receptor (GPCR). In some embodiments, composition further comprise a sequence encoding an affinity tag, optionally comprising a SNAP polypeptide. In some embodiments, the GPCR comprises a metabotropic glutamate receptor (mGluR), which is optionally, mGluR2. The disclosure also provides compositions and genetically modified cells comprising these vectors. Methods of treatment of retinal diseases and disorders comprising administering compositions, vectors, and cells of the disclosure to a subject in need are also provided.

Described are nucleic acid regulatory elements that are able to enhance liver-specific expression of genes, methods employing these regulatory elements and uses of these elements. Expression cassettes and vectors containing these nucleic acid regulatory elements are also disclosed. These are particularly useful for applications using gene therapy.

The invention pertains to an inducible CRISPR system for controlling expression of a CRISPR complex with an inducible fusion promoter. One embodiment of the invention provides HIV LTR-minimal Drosophila hsp70 fusion promoter that can be used for inducible co-expression of gRNA and Cas9 in HIV-infected cells to target cellular cofactors such as Cyclin T1. A single introduction of such embodiment leads to sustained suppression of HIV replication in stringent, chronically infected HeLa-CD4 cell lines as well as in T-cell lines. In another embodiment, the invention further relates to enhancement of HIV suppression by incorporating cis-acting ribozymes immediately upstream of the gRNA in the inducible CRISPR system construct. The inducible fusion promoter is adaptable for other tissue- or cell-type specific expression of the inducible CRISPR system.

The invention pertains to an inducible CRISPR system for controlling expression of a CRISPR complex with an inducible fusion promoter. One embodiment of the invention provides HIV LTR-minimal Drosophila hsp70 fusion promoter that can be used for inducible co-expression of gRNA and Cas9 in HIV-infected cells to target cellular cofactors such as Cyclin T1. A single introduction of such embodiment leads to sustained suppression of HIV replication in stringent, chronically infected HeLa-CD4 cell lines as well as in T-cell lines. In another embodiment, the invention further relates to enhancement of HIV suppression by incorporating cis-acting ribozymes immediately upstream of the gRNA in the inducible CRISPR system construct. The inducible fusion promoter is adaptable for other tissue- or cell-type specific expression of the inducible CRISPR system.

The present invention relates to methods and compositions for reducing the immunogenicity of chimeric Notch receptors, and specifically to transcription factors useful for controlling gene expression delivered to tissues by such chimeric Notch receptors.

The disclosure provides nucleic acids (comprising AAV expression cassettes), AAV vectors, and compositions for use in methods for treating and/or delaying the onset of diseases associated with mutations in the mecp2 gene, such as Rett Syndrome. Also, provided herein are methods for treating and/or delaying the onset of brain-derived neurotrophic factor (BDNF)-associated diseases.

A suspension useful for AAV9-mediated intrathecal and/or systemic delivery of an expression cassette containing a hIDS gene is provided herein. Also provided are methods and kits containing these vectors and compositions useful for treating Hunter syndrome and the symptoms associated with Hunter syndrome.

The present invention generally provides improved gene therapy vectors, cell-based compositions, and methods of using the same in methods of gene therapy. The present invention further provides improved gene therapy compositions for expanding hematopoietic cells and related methods for treatment of diseases, disorders, and conditions of the hematopoietic system such as thalassemias and anemias.