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 across the blood brain barrier comprising the step of systemically administering a rAAV9 comprising a self-complementary genome including the polynucleotide to a patient. 
     
     
         2 . A method of delivering a polynucleotide to the central nervous system comprising the step of systemically administering a rAAV9 comprising a self-complementary genome including the polynucleotide to a patient. 
     
     
         3 . The method of  claim 1  or  2  wherein the polynucleotide is delivered to brain. 
     
     
         4 . The method of  claim 1  or  2  wherein the polynucleotide is delivered to spinal cord. 
     
     
         5 . The method of  claim 1  or  2  wherein the polynucleotide is delivered to a glial cell. 
     
     
         6 . The method of  claim 5  wherein the glial cell is an astrocyte. 
     
     
         7 . The method of  claim 1  or  2  wherein the polynucleotide is delivered to a lower motor neuron. 
     
     
         8 . A method of delivering a polynucleotide to the peripheral nervous system comprising the step of administering a rAAV9 comprising a self-complementary genome including the polynucleotide to a patient. 
     
     
         9 . The method of  claim 8  wherein the polynucleotide is delivered to a nerve cell. 
     
     
         10 . The method of  claim 8  wherein the polynucleotide is delivered to a glial cell. 
     
     
         11 . A method of treating a neurodegenerative disease comprising the step of systemically administering a rAAV9 comprising a self-complementary genome including an survival motor neuron (SMN) polynucleotide to a patient. 
     
     
         12 . The method of  claim 11  wherein the neurodegenerative disease is spinal muscular atrophy. 
     
     
         13 . The method of  claim 11  wherein the neurodegenerative disease is amyotrophic lateral sclerosis. 
     
     
         14 . The method of  claim 11  wherein the SMN polynucleotide is delivered to an astrocyte. 
     
     
         15 . A rAAV9 with a self-complementary genome encoding SMN protein. 
     
     
         16 . A rAAV with a self-complementary genome encoding a trophic or protective factor. 
     
     
         17 . A method of delivering a polynucleotide to vascular endothelial cells comprising the step of systemically administering a rAAV9 comprising a self-complementary genome including the polynucleotide to a patient. 
     
     
         18 . A method of delivering a MECP2 polynucleotide to the central nervous system of a patient in need thereof comprising the step of administering a recombinant AAV9 (rAAV9) to the patient, wherein the rAAV9 comprises a methyl-CpG-binding protein 2 (MECP2) polynucleotide in a self-complementary genome. 
     
     
         19 . A method of treating Rett syndrome in a patient comprising the step of administering a recombinant AAV9 (rAAV9) to the patient, wherein the rAAV9 comprises a methyl-CpG-binding protein 2 (MECP2) polynucleotide in a self-complementary genome. 
     
     
         20 . A recombinant AAV9 with a self-complementary genome encoding methyl-CpG-binding protein 2.