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 . A method of delivering a polynucleotide encoding a therapeutic peptide for the treatment of mucopolysaccharidosis IIIA (MPS IIIA) to the central nervous system of a patient suffering from MPS IIIA, the method comprising administering a recombinant adeno-associated virus 9 (rAAV9) to the patient by direct intravenous injection, wherein the rAAV9 comprises the polynucleotide in a self-complementary genome. 
     
     
         2 . A method of treating mucopolysaccharidosis IIIA (MPS IIIA) in a patient suffering from MPS IIIA, the method comprising administering a rAAV9 to the patient by direct intravenous injection, wherein the rAAV9 comprises the polynucleotide in a self-complementary genome. 
     
     
         3 . The method of  claim 1  or  2  wherein the rAAV9 is delivered across the blood brain barrier (BBB) to the patient's central nervous system. 
     
     
         4 . The method of  claim 3  wherein the rAAV9 is delivered to the patient's brain. 
     
     
         5 . The method of  claim 3  wherein the rAAV9 is delivered to the patient's spinal cord. 
     
     
         6 . A method of delivering a polynucleotide encoding a therapeutic peptide for the treatment of mucopolysaccharidosis IIIB (MPS IIIB) to the central nervous system of a patient suffering from MPS IIIB, the method comprising administering a recombinant adeno-associated virus 9 (rAAV9) to the patient by direct intravenous injection, wherein the rAAV9 comprises the polynucleotide in a self-complementary genome. 
     
     
         7 . A method of treating mucopolysaccharidosis IIIB (MPS IIIB) in a patient suffering from MPS IIIB, the method comprising administering a rAAV9 to the patient by direct intravenous injection, wherein the rAAV9 comprises the polynucleotide in a self-complementary genome. 
     
     
         8 . The method of  claim 6  or  7 , wherein the rAAV9 is delivered across the blood brain barrier (BBB) to the patient's central nervous system. 
     
     
         9 . The method of  claim 8  wherein the rAAV9 is delivered to the patient's brain. 
     
     
         10 . The method of  claim 9 , wherein the rAAV9 is delivered to the patient's spinal cord. 
     
     
         11 - 20 . (canceled)