The present provides methods for treating spinal muscular atrophy using a self-complementary recombinant adeno-associated virus (rAAV) viral particle comprising a transgene expressing SMN. In one aspect, the viral particles are administered in the spinal column or cisterna magna in a human subject; for example, a pediatric human subject. Viral particles comprising AAV9 capsids are contemplated.

The present invention provides isolated promoters, transgene expression cassettes, vectors, kits, and methods for treatment of genetic diseases that affect the cone cells of the retina.

The present invention provides methods and compositions comprising an adeno-associated virus (AAV) capsid protein, comprising one or more amino acids substitutions, wherein the substitutions introduce a new glycan binding site into the AAV capsid protein.

Recombinant adeno-associated viral (AAV) capsid proteins are provided. Methods for generating the recombinant adeno-associated viral capsid proteins and a library from which the capsids are selected are also provided.

A CpG-modified recombinant adeno-associated viral (AAV) vector is described. The vector carries a nucleic acid molecule comprising AAV inverted terminal repeat (ITR) sequences and an exogenous gene sequence under the control of regulatory sequences which control expression of the gene product, in which the nucleic acid sequences carried by the vector are modified to significantly reduce CpG di-nucleotides such that an immune response to the vector is reduced as compared to the unmodified AAV vector. Also provided are methods and regimens for delivering transgenes using these AAV viral vectors, in which the innate immune response to the vector and/or transgene is significantly modulated.

Compositions, recombinant viruses, and recombinant viral vectors for inhibiting sarcolipin (SLN) expression or activity in a cell and for preventing or treating Duchenne Muscular Dystrophy (DMD) in a subject (e.g., a human patient having or predisposed to having DMD) and in some embodiments additionally cardiomyopathy, include a therapeutically effective amount of an inhibitor of SLN. Methods of using these compositions, recombinant viruses, and recombinant viral vectors are also described herein. These compositions, recombinant viruses, and recombinant viral vectors and methods of use provide novel therapies for DMD and associated cardiomyopathy based on the reduction of SLN expression and/or activity.

The present invention relates to compositions and methods comprising an engineered assembly activating protein (EAAP).

Disclosed herein are methods for systemically editing a gene in a subject and for systemically treating a genetic condition in a subject using a dual-vector CRISPR-Cas therapy. The methods comprise administering to the subject, via systemic administration, a gene editing AAV vector encoding a CRISPR effector protein (e.g., a Cas protein) and a targeting AAV vector providing one or more gRNAs targeted to the gene. In the methods, the ratio of the targeting AAV vector to the gene editing vector is greater than or equal to 2. Also provided are dual-vector systems for editing a gene or treating a genetic disease in a subject.

This document provides methods and materials involved in treating mammals having a neurological disorder in the brain (e.g., Alzheimer's disease). For example, methods and materials for administering a composition including exogenous nucleic acid encoding a NeuroD1 polypeptide to a mammal having a neurological disorder in the brain are provided.

The disclosure provides, in part, optimally-modified progranulin (PGRN) cDNA and associated genetic elements for use in recombinant adeno-associated virus (rAAV)-based gene therapy for neurodegenerative disorders characterized by cognitive disruption, behavioral impairment, and deficient lysosomal storage, including familial frontotemporal dementia (FTD), frontotemporal lobar degeneration (FTLD), neuronal ceroid lipofuscinosis (NCL), or Alzheimer's disease (AD).