Products and methods for delivery of polynucleotides by adeno-associated virus for lysosomal storage disorders

Abstract

The present invention relates to methods and materials useful for systemically delivering polynucleotides across the blood brain barrier using adeno-associated virus as a vector. For example, the present invention relates to methods and materials useful for systemically delivering α-N-acetylglucosamidinase polynucleotides to the central and peripheral nervous systems, as well as the somatic system. Use of these methods and materials is indicated, for example, for treatment of the lysosomal storage disorder mucopolysaccharidosis IIIB. As another example, the present invention relates to methods and materials useful for systemically delivering N-sulphoglucosamine sulfphohydrolase polynucleotides to the central and peripheral nervous systems, as well as the somatic system. Use of this second type of methods and materials is indicated, for example, for treatment of the lysosomal storage disorder mucopolysaccharidosis IIIA.

1 . A method of delivering an α-N-acetylglucosamidinase polynucleotide across the blood-brain-barrier comprising the step of systemically administering a rAAV9 comprising a single-stranded genome including the polynucleotide to a patient. 
     
     
         2 . A method of delivering an α-N-acetylglucosamidinase polynucleotide to the central nervous system comprising the step of systemically administering a rAAV9 comprising a single-stranded genome including the polynucleotide to a patient. 
     
     
         3 .- 7 . (canceled) 
     
     
         8 . A method of delivering an α-N-acetylglucosamidinase polynucleotide to the peripheral nervous system comprising the step of administering a rAAV9 comprising a single-stranded genome including the polynucleotide to a patient. 
     
     
         9 .- 10 . (canceled) 
     
     
         11 . A method of treating mucopolysaccharidosis IIIB comprising the step of systemically administering a rAAV9 comprising a single-stranded genome including an α-N-acetylglucosamidinase polynucleotide to a patient. 
     
     
         12 . The method of any one of  claim 1 ,  2 ,  8  or  11  wherein mannitol is administered prior to the administration of the rAAV. 
     
     
         13 . (canceled) 
     
     
         14 . A rAAV9 comprising a genome encoding α-N-acetylglucosamidinase. 
     
     
         15 . (canceled) 
     
     
         16 . A composition comprising the rAAV9 of  claim 14 . 
     
     
         17 . A method of delivering an N-sulphoglucosamine sulphohydrolase polynucleotide across the blood-brain-barrier comprising the step of systemically administering a rAAV9 or rh74 comprising a self-complementary genome including the polynucleotide to a patient. 
     
     
         18 . A method of delivering an N-sulphoglucosamine sulphohydrolase polynucleotide to the central nervous system comprising the step of systemically administering a rAAV9 or rh74 comprising a self-complementary genome including the polynucleotide to a patient. 
     
     
         19 .- 23 . (canceled) 
     
     
         24 . A method of delivering an N-sulphoglucosamine sulphohydrolase polynucleotide to the peripheral nervous system comprising the step of administering a rAAV9 or rh74 comprising a self-complementary genome including the polynucleotide to a patient. 
     
     
         25 .- 26 . (canceled) 
     
     
         27 . A method of treating mucopolysaccharidosis IIIA comprising the step of systemically administering a rAAV9 or rh74 comprising a self-complementary genome including an N-sulphoglucosamine sulphohydrolase polynucleotide to a patient. 
     
     
         28 . The method of any one of  claim 17 ,  18 ,  24  or  27  wherein mannitol is administered prior to the administration of the rAAV. 
     
     
         29 . (canceled) 
     
     
         30 . A rAAV9 or rh74 comprising a genome encoding N-sulphoglucosamine sulphohydrolase. 
     
     
         31 . A composition comprising the rAAV9 or rh74 of  claim 30 .