Sulfamidase (SGSH) variants, vectors, compositions and methods and uses for treating mucopolysaccharidosis type IIIA (MPS IIIA)
AssigneeThe Childeren's Hospital of Philadelphia
InventorsBeverly L. Davidson, Yonghong Chen
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Abstract
The invention relates to sulfamidase (SGSH) and SGSH variants. SGSH and SGSH variants can be delivered by way of a recombinant adeno-associated virus (rAAV) particle to a mammal's central nervous system (CNS) to transduce CNS cells that contact cerebrospinal fluid (CSF). Target mammals for SGSH and SGSH variant administration include mammals with a deficiency or defect in SGSH expression or function.
Claims54
A method of delivering sulfamidase (SGSH) to the central nervous system of a mammal, comprising administering to the mammal's central nervous system (CNS) a recombinant adeno-associated virus (rAAV) particle comprising a nucleic acid encoding a sulfamidase (SGSH) variant that is at least 90% identical to SEQ ID NO:
- 1 and has an amino acid substitution at position 264 of SEQ ID NO:
- 1, wherein the rAAV particle is injected at 1-5 locations in the brain effective to transduce cells that contact the cerebrospinal fluid (CSF) of the mammal such that the cells express and secrete the sulfamidase (SGSH) variant in the mammal.
A method of delivering sulfamidase (SGSH) to the central nervous system of a mammal, comprising administering to the mammal's brain parenchyma, subarachnoid space and/or intrathecal space a recombinant adeno-associated virus (rAAV) particle comprising a nucleic acid encoding a sulfamidase (SGSH) variant that is at least 90% identical to SEQ ID NO:1 and has an amino acid substitution at position 264 of SEQ ID NO:1, wherein the rAAV particle is injected at 1-5 locations in the brain in a manner effective to transduce brain parenchyma cells or cells that contact the cerebrospinal fluid (CSF) of the mammal such that the cells express and secrete the SGSH variant in the mammal.
A method of delivering sulfamidase (SGSH) to the central nervous system of a mammal, comprising administering to the mammal's central nervous system (CNS) a recombinant adeno-associated virus (rAAV) particle comprising a nucleic acid encoding a sulfamidase (SGSH) variant that is at least 90% identical to SEQ ID NO:
- 1 and has an amino acid substitution at position 264 of SEQ ID NO:
- 1, wherein the rAAV particle is injected at a single location in the brain effective to transduce cells that contact the cerebrospinal fluid (CSF) of the mammal such that the cells express and secrete the sulfamidase (SGSH) variant in the mammal.
A method of delivering sulfamidase (SGSH) to the central nervous system of a mammal, comprising administering to the mammal's brain parenchyma, subarachnoid space and/or intrathecal space a recombinant adeno-associated virus (rAAV) particle comprising a nucleic acid encoding a sulfamidase (SGSH) variant that is at least 90% identical to SEQ ID NO:1 and has an amino acid substitution at position 264 of SEQ ID NO:1, wherein the rAAV particle is injected at a single location in the brain in a manner effective to transduce brain parenchyma cells or cells that contact the cerebrospinal fluid (CSF) of the mammal such that the cells express and secrete the SGSH variant in the mammal.
A method of delivering sulfamidase (SGSH) to the central nervous system of a mammal, comprising administering to the mammal's central nervous system (CNS) a recombinant adeno-associated virus (rAAV) particle comprising a nucleic acid encoding a sulfamidase (SGSH) variant that is at least 90% identical to SEQ ID NO:
- 1 and has an amino acid substitution at position 264 of SEQ ID NO:
- 1, wherein the rAAV particle is administered to the:
- rostral lateral ventricle;
- and/or caudal lateral ventricle;
- and/or right lateral ventricle;
- and/or left lateral ventricle;
- and/or right rostral lateral ventricle;
- and/or left rostral lateral ventricle;
- and/or right caudal lateral ventricle;
- and/or left caudal lateral ventricle effective to transduce cells that contact the cerebrospinal fluid (CSF) of the mammal such that the cells express and secrete the sulfamidase (SGSH) variant in the mammal.
A method of delivering sulfamidase (SGSH) to the central nervous system of a mammal, comprising administering to the mammal's brain parenchyma, subarachnoid space and/or intrathecal space a recombinant adeno-associated virus (rAAV) particle comprising a nucleic acid encoding a sulfamidase (SGSH) variant that is at least 90% identical to SEQ ID NO:1 and has an amino acid substitution at position 264 of SEQ ID NO:1, wherein the rAAV particle is administered to the:
- rostral lateral ventricle;
- and/or caudal lateral ventricle;
- and/or right lateral ventricle;
- and/or left lateral ventricle;
- and/or right rostral lateral ventricle;
- and/or left rostral lateral ventricle;
- and/or right caudal lateral ventricle;
- and/or left caudal lateral ventricle in a manner effective to transduce brain parenchyma cells or cells that contact the cerebrospinal fluid (CSF) of the mammal such that the cells express and secrete the SGSH variant in the mammal.
Dependencies are inferred from the claim text.