Recombinant adeno-associated virus-mediated gene transfer via retroductal infusion of virions
OwnerAlan McClelland, Roland Scollayinventors
Life of this patent
Estimating the term…
Abstract
Methods for introducing recombinant adeno-associated virus (rAAV) virions into a cell or cells of a secretory gland are described. Recombinant AAV virions containing a heterologous gene are introduced into a duct of a secretory gland resulting in transduction of one or more secretory gland cells. Once a secretory gland cell is transduced by the rAAV virion, the heterologous gene is expressed and the expression product is then secreted. Exemplary examples of secretory glands are the liver, the submandibular gland, the parotid gland, and the sublingual gland. Using the methods of the invention, therapeutic levels of a protein are achieved. Methods for treating hemophilia are also disclosed.
Claims36
A method of delivering a protein to a mammal, comprising:
- a) providing recombinant adeno-associated virus (rAAV) virions, wherein said rAAV virions are free of helper virus, and wherein said rAAV virions comprise a heterologous gene encoding a protein;
- b) contacting said rAAV virions with a duct of a secretory gland of said mammal wherein said contacting results in transduction of at least one cell of said secretory gland;
- c) expressing said heterologous gene;
- and
- d) secreting said protein.
A method of delivering human Factor IX to a mammal, comprising:
- a) providing recombinant adeno-associated virus (rAAV) virions at a dose from about 1×109 to about 1×1011 rAAV viral genomes, wherein said rAAV virions are free of helper virus, and wherein said rAAV virions comprise a heterologous gene encoding human Factor IX;
- (b) contacting said rAAV virions with a duct of a salivary gland of said mammal wherein said contacting results in transduction of at least one cell of said duct of said salivary gland;
- (c) expressing said heterologous gene;
- and
- (d) secreting said human Factor IX into a blood vessel of said mammal.
A method of delivering human Factor IX to a mammal, comprising:
- a) providing recombinant adeno-associated virus (rAAV) virions at a dose from about 1×109to about 1×1011 rAAV viral genomes, wherein said rAAV virions are free of helper virus, and wherein said rAAV virions comprise a heterologous gene encoding human Factor IX;
- (b) contacting said rAAV virions with a duct of a liver of said mammal wherein said contacting results in transduction of at least one cell of said duct of said liver;
- (c) expressing said heterologous gene;
- and
- (d) secreting said human Factor IX into a blood vessel of said mammal wherein said human Factor IX is present in said blood vessel at a therapeutic level.
A method of treating hemophilia in a mammal, comprising:
- a) providing recombinant adeno-associated virus (rAAV) virions, wherein said rAAV virions are free of helper virus, and wherein said rAAV virions comprise a heterologous gene encoding a blood coagulation protein;
- b) contacting said rAAV virions with a duct of a secretory gland of said mammal wherein said contacting results in transduction of at least one cell of said secretory gland;
- c) expressing said heterologous gene;
- and
- d) secreting said blood coagulation factor into a blood vessel of said mammal wherein therapeutically effective levels of said blood coagulation factor are achieved.
Dependencies are inferred from the claim text.