Gene therapy delivery compositions and methods of use thereof
AssigneeWashington University
InventorsLogan Collins, David Curiel
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Abstract
Among the various aspects of the present disclosure is the provision of gene delivery compositions and methods of use thereof. Compositions of gene delivery matter that include adeno-associated viruses (AAVs) packaged inside vault proteins are described. Methods of treating a patient in need of a gene therapy using the disclosed AAVs packaged in vault proteins are also described.
Claims20
A composition for delivery of an AAV therapy, the composition comprising an adeno-associated virus (AAV) vector packaged inside a vault nanoparticle, wherein:
- a. the AAV vector comprises a protein capsid functionalized with a plurality of INT proteins;
- b. the vault nanoparticle comprises a plurality of MVP proteins;
- and
- c. an INT moiety of the AAV vector is covalently attached near an N-terminus of an MVP protein.
A method of treating a patient in need of an AAV therapy, the method administering a therapeutically effective amount of a composition comprising an adeno-associated virus (AAV) vector packaged inside a vault nanoparticle, wherein:
- a. the AAV vector comprises a protein capsid functionalized with a plurality of INT proteins;
- b. the vault nanoparticle comprises a plurality of MVP proteins;
- and
- c. an INT moiety of the AAV vector is covalently attached near an N-terminus of an MVP protein.
A method for producing an AAV therapy composition comprising an adeno-associated virus (AAV) vector packaged inside a vault nanoparticle, the method comprising:
- a. providing a plurality of AAV vectors, each AAV vector comprising a protein capsid functionalized with a plurality of SpyTag proteins flanked by first and second flexible linkers;
- b. providing a plurality of fusion proteins, each fusion protein comprising an INT protein covalently linked to a SpyCatcher protein by a third flexible linker;
- c. providing a plurality of vault nanoparticles comprising a plurality of MVT proteins;
- d. mixing the plurality of AAV vectors with the plurality of fusion proteins to form a plurality of INT-functionalized AAV vectors, each INT-functionalized AAV vector comprising an AAV vector and the SpyCatcher proteins of at least a portion of the fusion proteins covalently attached the SpyTag proteins of the protein capsid;
- and
- e. incubating the INT-functionalized AAV vectors with the plurality of vault nanoparticles to form the AAV therapy composition, wherein at least a portion of the INT proteins of each INT-functionalized AAV vector is covalently attached to at least a portion of the MVP proteins of each vault nanoparticle.
Dependencies are inferred from the claim text.