An isolated recombinant parvovirus vector comprising a synthetic enhancer comprising plurality of enhancer sequences operably linked to a promoter, and methods of using the vector, are provided.

The disclosure pertains to methods and compositions for treating disorders affecting the central nervous system (CNS). These disorders include neurometabolic disorders such as lysosomal storage diseases that affect the central nervous system, e.g., Niemann-Pick A disease. They also include disorders such as Alzheimer's disease. The disclosed methods involve contacting an axonal ending of a neuron with a composition containing high titer AAV carrying a therapeutic transgene so that the AAV vector is axonally transported in a retrograde fashion and transgene product is expressed distally to the administration site.

An isolated recombinant parvovirus vector comprising a synthetic enhancer comprising plurality of enhancer sequences operably linked to a promoter, and methods of using the vector, are provided.

The instant technology relates to a production system to produce AAV vectors in a serum free suspension platform and at high titers. This technology uses reagents comprising media, cells, transfection reagent, AAV enhancer, and a lysis buffer, each of which is designed to provide maximal AAV production from suspension culture of mammalian cells, e.g. HEK293 cells. With this new system we are able to deliver up to about 2?10.sup.11 viral genomes per milliliter (vg/mL) of unconcentrated AAV vectors.

Disclosed herein are viral vectors for use in recombinant molecular biology techniques. In particular, the present disclosure relates to self-limiting viral vectors comprising genes encoding site-specific endonucleases as well as recognition sequences for site-specific endonucleases such that expression of the endonuclease in a cell cleaves the viral vector and limits its persistence time. In some embodiments, the viral vectors disclosed herein also carry directives to delete, insert, or change a target sequence.

The instant technology relates to a production system to produce AAV vectors in a serum free suspension platform and at high titers. This technology uses reagents comprising media, cells, transfection reagent, AAV enhancer, and a lysis buffer, each of which is designed to provide maximal AAV production from suspension culture of mammalian cells, e.g. HEK293 cells. With this new system we are able to deliver up to about 210.sup.11 viral genomes per milliliter (vg/mL) of unconcentrated AAV vectors.

An isolated recombinant parvovirus vector comprising a synthetic enhancer comprising plurality of enhancer sequences operably linked to a promoter, and methods of using the vector, are provided.