The disclosure relates, in some aspects, to compositions and methods for treatment of diseases associated with aberrant lysosomal function, for example Parkinson's disease (PD) and Gaucher disease. In some embodiments, the disclosure provides expression constructs comprising a transgene encoding beta-Glucocerebrosidase (GBA) or a portion thereof alone or in combination with one or more PD-associated genes. In some embodiments, the disclosure provides methods of Parkinson's disease by administering such expression constructs to a subject in need thereof.

The disclosure relates, in some aspects, to compositions and methods for treatment of diseases associated with aberrant lysosomal function, for example Parkinson's disease (PD) and Gaucher disease. In some embodiments, the disclosure provides expression constructs comprising a transgene encoding beta-Glucocerebrosidase (GBA) or a portion thereof alone or in combination with one or more PD-associated genes. In some embodiments, the disclosure provides methods of Parkinson's disease by administering such expression constructs to a subject in need thereof.

The disclosure relates, in some aspects, to compositions and methods for treatment of diseases associated with aberrant lysosomal function, for example Parkinson's disease (PD) and Gaucher disease. In some embodiments, the disclosure provides expression constructs comprising a transgene encoding beta-Glucocerebrosidase (GBA) or a portion thereof alone or in combination with one or more PD-associated genes. In some embodiments, the disclosure provides methods of Parkinson's disease by administering such expression constructs to a subject in need thereof.

Provided herein are polynucleotides comprising novel bidirectional dual expression cassettes, recombination adeno-associated virus (rAAV) comprising these polynucleotides, and methods of making and using the polynucleotides and rAAV. Also provided are novel transcriptional control elements (e.g., promoters, enhancers, introns, polyadenylation sequences, and combinations thereof), and novel antibody coding sequences. The compositions and methods disclosed herein are particularly advantageous in that they allow for the efficient expression of two different polypeptides (e.g., an antibody heavy chain and an antibody light chain) in a cell. In particular, they allow for the efficient expression of antibodies (e.g., anti-C5 antibodies) in a subject, for the treatment of diseases (e.g., C5-mediated diseases, such as PNH).

A method of treating a retinal disease in a subject in need thereof, the method comprising administering to the subject a vector that comprises a mirtron for knocking down expression of a target gene expressed in the retina and a gene therapy vector comprising a mirtron for rhodopsin knock-down.

Provided herein are expression cassettes for expressing a transgene in a liver cell, wherein the transgene encodes a PAH polypeptide. Also provided are methods to treat phenylketonuria (PKU) and/or to reduce levels of phenylalanine in an individual in need thereof. Further provided herein are vectors (e.g., rAAV vectors), viral particles, pharmaceutical compositions and kits for expressing a PAH polypeptide in an individual in need thereof.

This document provides methods and materials for treating osteoarthritis. For example, a mammal having, or at risk for developing, osteoarthritis can be treated by increasing the level of one or more Klotho polypeptides (e.g., one or more alpha-Klotho (α-Klotho) polypeptides) within cells (e.g., chondrocytes) within the mammal.

The disclosure relates to compositions, methods, and processes for the preparation, use, and/or formulation of adeno-associated virus capsid proteins, wherein the capsid proteins comprise targeting peptide inserts for enhanced tropism to a target tissue.

The present invention provides an isolated nucleic acid molecule comprising, or consisting of, the nucleic acid sequence of SEQ ID NO:1 or a nucleic acid sequence of at least 400 bp having at least 80% identity to said sequence of SEQ ID NO:1, wherein said isolated nucleic acid molecule specifically leads to the expression in rod photoreceptors of a gene when operatively linked to a nucleic acid sequence coding for said gene.

The disclosure provides materials and methods useful in forming at least one bile duct or treating cholestatic disease or injury by transdifferentiating hepatocytes to cholangiocytes by delivery of an effective amount of an expressible Transforming Growth Factor β Type I Receptor (TGFBR1), Transforming Growth Factor β Type II Receptor (TGFBR2), SMAD3, SMAD1, SMAD2, SMAD5 or SMAD8/9, in either in vivo or in vitro environments. Another aspect provides a method of forming at least one bile duct or treating a cholestatic disease or injury by delivering an effective amount of JAG1, JAG2, DLL1, DLL3, DLL4, NOTCH1, NOTCH2, NOTCH3, NOTCH4 or the respective NOTCH intracellular domains either in vivo or in vitro. Also provided are methods for correcting mutant alleles of genes in the TGFβ and/or Notch pathways, e.g., JAG1 or NOTCH2, using ZFNs, TALENs, CRISPR or any other genome editing technique. Additionally, methods are provided for inducing increased expression of a normal, or wild-type, allele of a TGFβ or Notch pathway gene such as TGFBR1 or JAG1 using CRISPRa technology. Yet another aspect is drawn to a method of forming at least one bile duct or treating a cholestatic disease or injury by delivering an effective amount of a wild-type hepatocyte or a hepatocyte that has not been engineered to overexpress a gene product.