Abstract: Methods are disclosed for delivering a heterologous gene to a cell body of a neuron by contacting a muscle tissue innervated by the neuron with a viral vector comprising a heterologous gene, wherein the viral vector enters said neuron and is retrogradely moved to the cell body. Additionally, methods for expressing secreted proteins from a nerve cell body as well as methods for treating neurodegenerative disorders such as amyotrophic lateral sclerosis are described.

Abstract: The present invention provides mutant adeno-associated virus (AAV) that exhibit altered capsid properties, e.g., reduced binding to neutralizing antibodies in serum and/or altered heparin binding and/or altered infectivity of particular cell types. The present invention further provides libraries of mutant AAV comprising one or more mutations in a capsid gene. The present invention further provides methods of generating the mutant AAV and mutant AAV libraries, and compositions comprising the mutant AAV. The present invention further provides recombinant AAV (rAAV) virions that comprise a mutant capsid protein. The present invention further provides nucleic acids comprising nucleotide sequences that encode mutant capsid proteins, and host cells comprising the nucleic acids. The present invention further provides methods of delivering a gene product to an individual, the methods generally involving administering an effective amount of a subject rAAV virion to an individual in need thereof.