HSP104 variants and uses thereof
View Patent ↗Protein misfolding underpins several fatal neurodegenerative disorders. The application is directed to recombinant Hsp104 proteins comprising missense mutations aimed at correcting these events, and methods for expressing and delivering same.
1. A recombinant Hsp104 protein of wild type amino acid sequence of SEQ ID NO: 1, wherein said sequence comprises a missense mutation, wherein said missense mutation is A503C, A503D, A503E, A503F, A503G, A503H, A503I, A503K, A503L, A503M, A503N, A503Q, A503R, A503S, A503T, A503V, A503W, or A503Y, wherein said sequence further comprises mutation in the substrate-binding pore loops where said mutation in the substrate binding loop comprises a Y257F and Y662F.
2. The recombinant protein of claim 1 , wherein said missense mutation is A503C, A503G, A503S, or A503V.
3. A recombinant Hsp104 protein of wild type amino acid sequence of SEQ ID NO: 1, wherein said sequence comprises mutations A503V, Y257F, and Y662F.
4. A method for suppressing proteotoxicity in a mammal in need thereof, comprising administering the recombinant protein of claim 1 .
5. A composition comprising the recombinant protein of claim 1 and a pharmaceutically acceptable carrier.
6. A method for suppressing proteotoxicity in a mammal in need thereof, comprising administering the composition of claim 5 .
7. A method for suppressing proteotoxicity in a mammal in need thereof, comprising administering the recombinant protein of claim 2 .
8. A composition comprising the recombinant protein of claim 2 and a pharmaceutically acceptable carrier.
9. A method for suppressing proteotoxicity in a mammal in need thereof, comprising administering the composition of claim 8 .
10. A method for suppressing proteotoxicity in a mammal in need thereof, comprising administering the recombinant protein of claim 3 .
11. A composition comprising the recombinant protein of claim 3 and a pharmaceutically acceptable carrier.
12. A method for suppressing proteotoxicity in a mammal in need thereof, comprising administering the composition of claim 11 .
13. The recombinant protein of claim 2 , wherein said missense mutation is A503S.
14. The recombinant protein of claim 13 , wherein said sequence comprises mutations Y257F and Y662F.
15. A method for suppressing proteotoxicity in a mammal in need thereof, comprising administering the recombinant protein of claim 13 .
16. A composition comprising the recombinant protein of claim 13 and a pharmaceutically acceptable carrier.
17. A method for suppressing proteotoxicity in a mammal in need thereof, comprising administering the composition of claim 16 .