TATk-CDKL5 fusion proteins, compositions, formulations, and use thereof
View Patent ↗Disclosed herein are compositions and formulations containing a TATk-CDKL5 fusion protein. Also disclosed are methods of producing a TATk-CDKL5 fusion protein from vectors containing a TATk-CDKL5 cDNA and methods of transducing cells with the vectors containing a TATk-CDKL5 cDNA and the TATk-CDKL5 fusion protein.
1. A method of treating a CDKL5 deficiency, Rett syndrome or a Rett syndrome variant, the method comprising administering a fusion protein to a subject in need thereof, wherein the fusion protein comprises:
a CDKL5 polypeptide sequence, wherein the CDKL5 polypeptide sequence comprises SEQ ID NO: 2; and
a TATκ polypeptide sequence, wherein the TATκ polypeptide sequence comprises SEQ ID NO: 4, wherein the TATκ polypeptide is operatively coupled to the CDKL5 polypeptide.
2. The method of claim 1 , wherein the fusion protein further comprises an Igk-chain leader sequence polypeptide, wherein the Igk-chain leader sequence is operatively coupled to the CDKL5 polypeptide.
3. The method of claim 1 , wherein the fusion protein further comprises a reporter protein polypeptide, wherein the reporter protein polypeptide is operatively coupled to the CDKL5 polypeptide.
4. The method of claim 1 , wherein the fusion protein further comprises a protein tag polypeptide, wherein the protein tag polypeptide is operatively coupled to the CDKL5 polypeptide.
5. The method of claim 1 , wherein the fusion protein has a polypeptide sequence comprising SEQ ID NO: 8 or SEQ ID NO: 10.
6. The method of claim 1 , wherein administering the fusion protein increases neurite growth, elongation, branch number, or branch density in the brain of a treated subject as compared to an untreated control subject.
7. The method of claim 1 , wherein administering the fusion protein reduces neuron apoptosis in the brain of a treated subject as compared to an untreated control subject.
8. The method of claim 1 , wherein the subject has a CDKL5 deficiency.
9. The method of claim 1 , wherein the subject has Rett syndrome.
10. The method of claim 1 , wherein the subject has a Rett syndrome variant.
11. A method of treating a CDKL5 deficiency, Rett syndrome or a Rett syndrome variant, the method comprising administering a fusion protein to a subject in need thereof, wherein the fusion protein comprises:
a CDKL5 polypeptide sequence, wherein the CDKL5 polypeptide sequence comprises SEQ ID NO: 16; and
a TATκ polypeptide sequence, wherein the TATκ polypeptide sequence comprises SEQ ID NO: 4, wherein the TATκ polypeptide is operatively coupled to the CDKL5 polypeptide.
12. The method of claim 11 , wherein the fusion protein further comprises an Igk-chain leader sequence polypeptide, wherein the Igk-chain leader sequence is operatively coupled to the CDKL5 polypeptide.
13. The method of claim 11 , wherein the fusion protein further comprises a reporter protein polypeptide, wherein the reporter protein polypeptide is operatively coupled to the CDKL5 polypeptide.
14. The method of claim 11 , wherein the fusion protein further comprises a protein tag polypeptide, wherein the protein tag polypeptide is operatively coupled to the CDKL5 polypeptide.
15. The method of claim 11 , wherein the fusion protein has a polypeptide sequence comprising SEQ ID NO: 12 or SEQ ID NO: 14.
16. The method of claim 11 , wherein administering the fusion protein increases neurite growth, elongation, branch number, or branch density in the brain of a treated subject as compared to an untreated control subject.
17. The method of claim 11 , wherein administering the fusion protein reduces neuron apoptosis in the brain of a treated subject as compared to an untreated control subject.
18. The method of claim 11 , wherein the subject has a CDKL5 deficiency.
19. The method of claim 11 , wherein the subject has Rett syndrome.
20. The method of claim 11 , wherein the subject has a Rett syndrome variant.