Guided injections for aav gene transfer to muscle
AssigneeResearch Institute At Nationwide Children's Hospital
InventorsJerry R. MENDELL, Brian K. KASPAR, Samiah AL-ZAIDY
Life of this patent
Estimating the term…
Abstract
The disclosure relates to methods for treating subjects with musculoskeletal diseases or with muscle wasting not associated with a musculoskeletal disease by gene transfer with recombinant adeno-associated viruses (rAAV) encoding myostatin inhibitors such as follistatin-344. The rAAV are administered prior to development of diffuse muscle fibrosis in a subject, or the rAAV administration avoids regions of muscle fibrosis in a subject.
Claims12
A method of enhancing muscle function in a subject with a musculoskeletal disease or with muscle wasting not associated with a musculoskeletal disease comprising the step of administering to the subject by one or more intramuscular injections a composition comprising infectious encapsidated rAAVs, each rAAV comprising a rAAV genome comprising AAV inverted terminal repeats flanking a polynucleotide encoding follistatin-344, wherein the polynucleotide is operatively linked to transcriptional control DNA and wherein the genome lacks AAV rep and cap DNA,
- wherein the administration is prior to development of diffuse muscle fibrosis in the subject or wherein the intramuscular injection or injections avoid regions of muscle fibrosis in the subject.
A method of enhancing muscle function in a subject with Becker muscular dystrophy comprising the step of administering to the subject by one or more intramuscular injections a composition comprising infectious encapsidated rAAVs, each rAAV comprising a rAAV genome comprising AAV inverted terminal repeats flanking a polynucleotide encoding follistatin-344, wherein the polynucleotide is operatively linked to transcriptional control DNA and wherein the genome lacks AAV rep and cap DNA, wherein the rAAV dose injected is at least about 6×1011 vg/kg/leg or 1.2e12 vg/kg/subject.
A method of enhancing muscle function in a subject with Duchenne muscular dystrophy comprising the step of administering to the subject by one or more intramuscular injections a composition comprising infectious encapsidated rAAVs, each rAAV comprising a rAAV genome comprising AAV inverted terminal repeats flanking a polynucleotide encoding follistatin-344, wherein the polynucleotide is operatively linked to transcriptional control DNA and wherein the genome lacks AAV rep and cap DNA, wherein the rAAV dose injected is at least about 2×1011 vg/kg/leg or at least about 6e11 vg/kg/subject.
A method of enhancing muscle function in a subject with inclusion body myositis comprising the step of administering to the subject by one or more intramuscular injections a composition comprising infectious encapsidated rAAVs, each rAAV comprising a rAAV genome comprising AAV inverted terminal repeats flanking a polynucleotide encoding follistatin-344, wherein the polynucleotide is operatively linked to transcriptional control DNA and wherein the genome lacks AAV rep and cap DNA, wherein the rAAV dose injected is at least about 1.2e12 vg/kg/limb.
Dependencies are inferred from the claim text.