Aav variants for the treatment of dry amd
AssigneeAdverum Biotechinologies, Inc.
InventorsRuslan Grishanin, Gustavo De Alencastro, Brigit Riley
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Abstract
Provided is the intravitreal administration of recombinant adeno-associated virus (rAAV)-based gene therapies for the amelioration of dry-AMD related symptoms, prevention of dry-AMD and treatment of dry-AMD.
Claims31
A polynucleotide cassette for increasing the concentration of human CFI in the vitreous humor and/or retinal extracellular space of a mammalian eye, comprising:
- a. an enhancer and promoter region;
- b. a chimeric intron;
- c. a Kozak sequence
- d. a unique coding sequence optimized for increased expression and low CpG, operatively linked to the promoter region wherein the coding sequence is a human CFI gene,
- e. a human scaffold attachment region;
- and
- f. a polyadenylation site.
A method of increasing the concentration of human CFI in the vitreous humor and/or retinal extracellular space of a mammalian eye, comprising administering to a subject a recombinant adeno-associated virus (rAAV) vector at a dosage ranging from about 1E9 to about 4E12 vector genomes (vg)/eye, wherein the rAAV vector comprises an AAV2 capsid variant and wherein the rAAV vector comprises a polynucleotide cassette comprising:
- a. An enhancer and promoter region;
- b. a chimeric intron;
- c. a Kozak sequence
- d. a unique coding sequence optimized for increased expression and low CpG, operatively linked to the promoter region wherein the coding sequence is a human CFI gene,
- e. a human scaffold attachment region;
- and
- f. a polyadenylation site.
A polynucleotide cassette for increasing the concentration of human CFI in a mammalian eye, comprising:
- a. an enhancer and promoter region;
- b. a chimeric intron;
- c. a Kozak sequence
- d. a unique coding sequence optimized for increased expression and low CpG, operatively linked to the promoter region wherein the coding sequence is a human CFI gene,
- e. a human scaffold attachment region;
- and
- f. a polyadenylation site.
The polynucleotide cassette of claim 24, wherein said polynucleotide cassette is for increasing the concentration of human CFI in the vitreous humor and/or retinal extracellular space of a mammalian eye.
A method of treating dry acute macular degeneration (dry-AMD) in a human subject, comprising administering to a subject in need thereof a therapeutically effective amount of recombinant adeno-associated virus (rAAV) vector, wherein the rAAV vector comprises an AAV2 capsid variant and a polynucleotide cassette comprising:
- a. An enhancer and promoter region;
- b. a chimeric intron;
- c. a Kozak sequence
- d. a unique coding sequence optimized for increased expression and low CpG, operatively linked to the promoter region wherein the coding sequence is a human CFI gene,
- e. a human scaffold attachment region;
- and
- f. a polyadenylation site.
The method of claim 26, wherein the rAAV vector is administered intravitreally.
Dependencies are inferred from the claim text.