Recombinant adeno-associated virus delivery of alpha-sarcoglycan polynucleotides
AssigneeNationwide Children's Hospital, Inc.
InventorsJerry R. Mendell, Louis Chicoine, Louise Rodino-Klapac, Kelly Reed Clark, Thomas J. Preston
Life of this patent
Estimating the term…
Abstract
The present invention relates to recombinant adeno-associated virus (rAAV) delivery of an alpha-sarcoglycan gene. The invention provides rAAV products and methods of using the rAAV in the treatment of limb girdle muscular dystrophies such as LGMD2D.
Claims7
A method of improving muscle function in a patient afflicted with limb girdle muscular dystrophy type 2D (LGMD 2D) comprising the step of perfusing the vasculature of a limb of the patient with an infectious encapsidated recombinant adeno-associated virus (AAV) comprising a AAVrh.74 capsid polynucleotide of SEQ ID NO:2, wherein the genome of the recombinant AAV comprises a gene expression cassette comprising the polynucleotide of SEQ ID NO:
- 3 encoding an alpha-sarcoglycan under the transcriptional control of a promoter, said cassette flanked by one or more AAV inverted terminal repeats, and wherein the genome lacks AAV rep and cap DNA.
A method of delivering an alpha-sarcoglycan polynucleotide to an animal in need thereof, comprising the step of perfusing the vasculature of a limb of the animal with an infectious encapsidated recombinant AAV comprising a AAVrh.74 capsid polynucleotide of SEQ ID NO:2, wherein the genome of the recombinant AAV comprises a gene expression cassette comprising the polynucleotide of SEQ ID NO:
- 3 encoding an alpha-sarcoglycan under the transcriptional control of a promoter, said cassette flanked by one or more AAV inverted terminal repeats, and wherein the genome lacks AAV rep and cap DNA.
An infectious encapsidated recombinant AAV comprising a AAVrh.74 capsid polynucleotide of SEQ ID NO:
- 2, wherein the genome of the recombinant AAV comprises a gene expression cassette comprising the polynucleotide of SEQ ID NO:
- 3 encoding an alpha-sarcoglycan under the transcriptional control of a promoter, said cassette flanked by one or more AAV inverted terminal repeats, and wherein the genome lacks AAV rep and cap DNA.
A method of delivering a recombinant adeno-associated virus (AAV) comprising:
- connecting a recirculation circuit to a vasculature of a limb;
- isolating circulation of the limb from the remainder of the body;
- adding to the recirculation circuit an infectious encapsidated recombinant AAV comprising a AAVrh.74 capsid polynucleotide of SEQ ID NO:2, wherein the genome of the recombinant AAV comprises a gene expression cassette comprising the polynucleotide of SEQ ID NO:
- 3 encoding an alpha-sarcoglycan under the transcriptional control of a promoter, said cassette flanked by one or more AAV inverted terminal repeats, and wherein the genome lacks AAV rep and cap DNA;
- passing the recombinant AAV through the recirculation circuit and the limb repeatedly;
- and
- disconnecting the recirculation circuit from the limb.
Dependencies are inferred from the claim text.