Patent

1. A dual promoter lentivirus vector that expresses 1) a protein of interest, wherein the protein of interest is encoded by a transgene and wherein the protein of interest is associated with a lysosomal storage disorder and 2) a mutant form of inosine-5′-monophosphate dehydrogenase 2 (IMPDH2(IY)), wherein the lentivirus vector when transduced into a host cell confers resistance to mycophenolic acid (MPA) and/or mycophenolate mofetil (MMF) in vitro and/or in vivo and, wherein the mutant form of IMPDH2(IY) is encoded by the nucleotide sequence of SEQ ID NO: 7, or a sequence having at least 85% sequence identity to the nucleotide sequence of SEQ ID NO: 7.

2. The dual promoter lentivirus vector of claim 1 , wherein the host cell is a hematopoietic cell.

3. The dual promoter lentivirus vector of claim 1 , wherein a first promoter is hPGK promoter and a second promoter is EF1α promoter.

4. The dual promoter lentivirus vector of claim 1 , wherein the protein of interest is α-galactosidase A and the lysosomal storage disorder is Fabry disease.

5. The dual promoter lentivirus vector of claim 4 , wherein the α-galactosidase A is encoded by the transgene AGA comprising the nucleotide sequence of SEQ ID NO: 5 or a nucleotide sequence having 80% sequence identity to the nucleotide sequence of SEQ ID NO: 5.

6. The dual promoter lentivirus vector of claim 4 , wherein the lentivirus vector is encoded by the nucleotide sequence of SEQ ID NO: 3 or a nucleotide sequence having 80% sequence identity to the nucleotide sequence of SEQ ID NO: 3.

7. The dual promoter lentivirus vector of claim 1 , wherein the protein of interest is glucocerebrosidase (GBA protein).

8. The dual promoter lentivirus vector of claim 7 , wherein the glucocerebrosidase is encoded by the transgene GBA comprising the nucleotide sequence of SEQ ID NO: 6 or a nucleotide sequence having 80% sequence identity to the nucleotide sequence of SEQ ID NO: 6.

9. The dual promoter lentivirus vector of claim 7 , wherein the lentivirus vector is encoded by the nucleotide sequence of SEQ ID NO: 3 or a nucleotide sequence having 80% sequence identity to the nucleotide sequence of SEQ ID NO: 4.

10. The dual promoter lentivirus vector of claim 1 , wherein the protein of is acid ceramidase (ASAH1).

11. The dual promoter lentivirus vector of claim 10 , wherein the ASAH1 is encoded by the transgene comprising the nucleotide sequence of SEQ ID NO: 8 or a nucleotide sequence having 80% sequence identity to the nucleotide sequence of SEQ ID NO: 8.

12. The dual promoter lentivirus vector of claim 1 , wherein the protein of interest is α-glucosidase (GAA).

13. The dual promoter lentivirus vector of claim 12 , wherein the GAA is encoded by the transgene comprising the nucleotide sequence of SEQ ID NO: 9 or a nucleotide sequence having 80% sequence identity to the nucleotide sequence of SEQ ID NO: 9.

14. A host cell expressing the dual promoter lentivirus vector of claim 1 .

15. The host cell of claim 14 , wherein the host cell is a hematopoietic cell.

16. A method of treating a subject having a lysosomal storage disease (LSD) associated with a defect in a single protein, the method comprising the steps of:

i) transducing hematopoietic stem cells (HSCs) obtained from a subject or a suitable donor in vitro or ex vivo with the dual promoter lentivirus vector of claim 1 ,

ii) introducing the transduced HSCs into the subject to produce a population of lentivirus vector transduced HSCs engrafted in the subject, and

(iii) administering to the subject an amount of mycrophenolate mofetil (MMF) sufficient to enrich the population of lentivirus vector transduced HSCs engrafted in the subject, wherein the method treats one or more symptoms of the lysosomal storage disease or disorder.

17. The method of claim 16 , wherein the protein of interest is selected from the group consisting of α-galactosidase A, glucocerebrosidase (GBA protein), ASAH1, or GAA.

18. The method of claim 16 , wherein the subject is in need of treatment for Fabry disease, and wherein the dual promoter lentivirus vector expresses α-galactosidase A and IMPDH2(IY) in the transduced HSCs, and wherein the method treats one or more symptoms of Fabry disease.

19. The method of claim 16 , wherein the dual promoter lentiviral vector comprises the nucleotide sequence of SEQ ID NO: 3 or a nucleotide sequence having at least 80% sequence identity to the nucleotide sequence of SEQ ID NO: 3, wherein the lysosomal storage disease is Fabry disease.

20. The method of claim 16 , wherein the dual promoter lentivirus vector expresses glucocerebrosidase and IMPDH2(IY) in the transduced HSCs, and wherein the method treats one or more symptoms of Gaucher disease.

21. The method of claim 20 , wherein the dual promoter lentivirus vector comprises the nucleotide sequence of SEQ ID NO: 4 or a nucleotide sequence having at least 80% sequence identity to the nucleotide sequence of SEQ ID NO: 4.

22. The method of claim 16 , wherein the subject is in need of treatment for Fabry disease, and wherein the dual promoter lentivirus vector expresses ASAH1 and IMPDH2(IY) in the transduced HSCs, and wherein the method treats one or more symptoms of Farber disease.

23. The method of claim 16 , wherein the subject is in need of treatment for Fabry disease, and wherein the dual promoter lentivirus vector expresses GAA and IMPDH2(IY) in the transduced HSCs, and wherein the method treats one or more symptoms of Pompe disease.

24. The method of claim 16 , wherein the transduced HSCs are injected into the patient.

25. The method of claim 16 , wherein the MMF is administered in an amount of 0.1-5 mg/kg three times a day.

26. The method of claim 16 , wherein the MMF is administered at 5-10 mg/kg three times a day or 1000 mg twice a day.