Delivery of polynucleotides using recombinant aav9

Abstract

The present invention relates to Adeno-associated virus 9 methods and materials useful for systemically delivering polynucleotides across the blood brain barrier. Accordingly, the present invention also relates to methods and materials useful for systemically delivering polynucleotides to the central and peripheral nervous systems. The present invention also relates to Adeno-associated virus type 9 methods and materials useful for intrathecal delivery of polynucleotides. Use of the methods and materials is indicated, for example, for treatment of lower motor neuron diseases such as spinal muscle atrophy and amyotrophic lateral sclerosis as well as Pompe disease and lysosomal storage disorders. Use of the methods and materials is also indicated, for example, for treatment of Rett syndrome.

1 - 20 . (canceled) 
     
     
         21 . A method of treating Rett syndrome in a patient comprising the step of intrathecal administration of an effective dose of a recombinant AAV9 (rAAV9) to the patient, wherein the rAAV9 comprises a methyl-CpG-binding protein 2 (MECP2) polynucleotide in a self-complementary genome. 
     
     
         22 . The method of  claim 21  wherein the patient is a female patient. 
     
     
         23 . The method of  claim 21  wherein the dose of rAAV9 administered is 1×10 11  vg/kg or more. 
     
     
         24 . The method of  claim 21  wherein the MECP2 polynucleotide is expressed in neuronal and glial cells in the central nervous system of the patent. 
     
     
         25 . The method of  claim 21  wherein the treatment reduces patient seizures. 
     
     
         26 . The method of  claim 21  wherein the treatment improves patient mobility.