The present invention relates to synthetic retinal ON-bipolar cell-specific promoter sequences and their use in therapeutic transgene delivery to the eye for the improvement and/or restoration of vision. The invention features metabotropic glutamate receptor 6 (mGluR6) promoters for an increased and more specific expression in ON-bipolar cells, in particular in cone ON-bipolar cells of the human macula.

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

In certain embodiments a lentiviral vector for the treatment of Wiskott-Aldrich Syndrome (WAS) is provided. In certain embodiments the vector comprises an expression cassette comprising a nucleic acid construct comprising an effective fragment of the endogenous promoter of the WAS gene where said promoter has maximum length of 600 bp and contains the sequence of HS1pro, and a nucleic acid that encodes the Wiskott-Aldrich Syndrome protein (WASp) operably linked to the effective fragment of the endogenous promoter of the WAS gene.

In certain embodiments a lentiviral vector for the treatment of X-linked chronic granulomatous disease (X-CGD) is provided. In certain embodiments the vector comprises an expression cassette comprising a nucleic acid construct comprising a CYBB promoter or effective fragment thereof; and a nucleic acid that encodes gp91.sup.phox operably linked to the CYBB promoter or promoter fragment.

Disclosed herein are invariant natural killer T (iNKT) cells engineered using hematopoietic stem and progenitor cells (HSPCs) and methods of making and using thereof.

Provided is a nucleic acid construct for expressing a gene of interest, the nucleic acid construct comprising, in order from 5′-terminus, each sequence of: (a) a 5′ long terminal repeat (LTR) sequence derived from a retrovirus; (b) a packaging signal sequence (IV) derived from a retrovirus; (c) a sequence or multiple cloning site of the gene of interest; (d) a post-transcriptional regulatory sequence (PRE); (e) an siRNA generating sequence which forms at least one stem-loop structure and in which RNA, which induces RNA interference in mammalian cells, is transcribed; and (f) a 3′ LTR sequence derived form a retrovirus.

Described herein are compositions comprising AAV vectors comprising a sequence encoding mucolipin 1, and methods of use thereof for gene therapy of Mucolipidosis IV (MLIV).

Disclosed herein are novel variants of KCVN2 and their use, for example, in methods of treating a subject with a retinal disorder, such as CDSRR.

The present disclosure provides, among other things, a recombinant adeno-associated virus (rAAV) vector comprising an AAV8 capsid and a codon-optimized sequence encoding a human phenylalanine hydroxylase (PAH) enzyme. The disclosure also provides a method of treating a subject having phenylketonuria (PKU), comprising administering to the subject in need thereof a recombinant adeno-associated vims (rAAV) vector comprising an AAV8 capsid, and a promoter operably linked to a nucleic acid sequence that encodes PAH, and wherein administering results in a decrease in phenylalanine level in the subject.

Fragile X syndrome (FXS) is the most common inherited form of human intellectual disability. FXS is caused by loss of function of the FMR1 gene which results in significant behavioral deficits in spatial learning and memory tests. FMR1−/− knockout mice share many of the learning deficits and decreased synaptic function encountered in FXS patients. Anecdotal evidence indicates a reduction in the amount of Reelin, a large extracellular signaling protein important for normal hippocampal synaptic plasticity, may play role in the etiology of FXS. Disclosed herein is a rAAV9 Reelin viral vector expressing a REELIN repeat R3+R6 fusion protein that is shown to rescue cognitive deficits in FMR1−/− mice as evaluated in the Hidden Platform Water Maze, Open Field and Fear Conditioning. Reelin gene therapy is therefore potentially a novel therapeutic for the treatment of Fragile X Syndrome.