The invention provides a platform and methods of using the platform for the regulation of the expression of a target gene using exposure to an aptamer ligand (for example, a small molecule). The platform features a polynucleotide gene regulation cassette that is placed in the target gene and includes a synthetic riboswitch positioned in the context of a 5′ intron-alternative exon-3′ intron. The riboswitch comprises an effector region and a sensor region (e.g., an aptamer that binds a small molecule ligand) such that the alternative exon is spliced into the target gene mRNA when the ligand is not present thereby preventing expression of the target gene. When the ligand is present, the alternative exon is not spliced into the target gene mRNA thereby providing expression of the target gene.

The present disclosure provides methods of treating a human having a disease or disorder that would benefit from increasing platelet counts. The method involves inhibiting the enzyme activity of biliverdin IXβ reductase (BLVRB) activity or inhibiting the expression of BLVRB gene.

Provided herein are improved gene therapy vectors and methods of use, in some embodiments, comprising sequences for improved expression and cellular targeting of a therapeutic protein.

Nucleic acid constructs and compositions that allow insertion and/or expression of a retinoschisin coding sequence are provided. Nuclease agents targeting RS1 loci are provided. Compositions and methods of using such constructs for integration into a target genomic locus and/or expression in a cell are also provided. Methods of treating X-linked juvenile retinoschisis using the nucleic acid constructs and compositions are also provided.

The present disclosure provides, among other things, polynucleotide constructs, compositions, and methods of treating ornithine transcarbamylase deficiency, including administering to a subject in need thereof a composition comprising a polynucleotide construct comprising a 5′ UTR, a codon optimized mRNA encoding an ornithine transcarbamylase, and a 3′ UTR.

Embodiments of the disclosure encompass systems, methods, and compositions related to selective advantages to somatic cells that harbor one or more particular genetic modifications. In particular embodiments, there is selective expansion of gene-targeted cells wherein the strategy involves deletion of an essential gene product that is replaced with targeted integration that also includes integration of a therapeutic transgene. The cells that harbor the replaced essential gene product, and thereby the therapeutic transgene, are selected for using pharmaceutical or nutritional agents that are linked to the function of the essential gene product.

The present invention provides methods and compositions comprising an adeno-associated vims (AAV) synthetic inverted terminal repeat (ITR), wherein the ITR may have modified promoter transcriptional function. Additionally provided are vectors and virus particles comprising the same, as well as methods of their use.

In certain embodiments, the disclosure relates to compositions and methods relating to a translation-based gene regulation system that functions in mammalian cells. In certain specific embodiments, the disclosure relates to methods of regulating gene expression via modulating translation termination.

The invention relates to compositions including polynucleotides encoding polypeptides which have been chemically modified by replacing the uridines with 1-methyl-pseudouridine to improve one or more of the stability and/or clearance in tissues, receptor uptake and/or kinetics, cellular access by the compositions, engagement with translational machinery, mRNA half-life, translation efficiency, immune evasion, protein production capacity, secretion efficiency, accessibility to circulation, protein half-life and/or modulation of a cell's status, function, and/or activity.

The present application provides materials and methods for treating a patient with one or more condition associated with FXN whether ex vivo or in vivo. In addition, the present application provides materials and methods for editing and/or modulating the expression of FXN gene in a cell by genome editing.