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1. WO2020163408 - NANOPARTICULES LIPIDIQUES FUSOGÈNES POUR LA PRODUCTION SPÉCIFIQUE À UNE CELLULE CIBLE DE PROTÉINES THÉRAPEUTIQUES INDUCTIBLES PAR LA RAPAMYCINE

Note: Texte fondé sur des processus automatiques de reconnaissance optique de caractères. Seule la version PDF a une valeur juridique

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CLAIMS

What is claimed is:

1. An expression construct for targeted production of a therapeutic protein within a target cell, said expression construct comprising:

a. a transcriptional promoter that is activated in response to one or more factors each of which is produced within a target cell; and

b. a nucleic acid that is operably linked to and under regulatory control of said transcriptional promoter, wherein said nucleic acid encodes a therapeutic protein that can reduce, prevent, and/or eliminate the growth and/or survival of a cell, including said target cell.

2. The expression construct of claim 1 wherein said transcriptional promoter is activated in said target cell but is not activated in a normal mammalian cell that is not associated with said disease.

3. The expression construct of claim 2 wherein at least one of said factors is not produced in said normal mammalian cell that is not associated with said disease.

4. The expression construct of claim 3 wherein said normal mammalian cell is a normal human cell.

5. The expression construct of claim 4 wherein said normal human cell is selected from the group consisting of a normal skeletal myoblast, a normal adipose cell, a normal cell of the eye, a normal brain cell, a normal liver cell, a normal colon cell, a normal lung cell, a normal pancreas cell, and/or a normal heart cell, which normal cell is not associated with disease, condition, or aging.

6. The expression construct of claim 1 wherein said target cell is selected from the group consisting of a mammalian cell and a bacterial cell.

7. The expression construct of claim 6 wherein said target cell is a mammalian cell.

8. The expression construct of claim 7 wherein said mammalian target cell is a human cell selected from the group consisting of a senescent cell, a cancer cell, and a cell that is infected with an infectious disease agent.

9. The expression construct of claim 8 wherein said human target cell is a senescent cell.

10. The expression construct of claim 9 wherein said transcriptional promoter is selected from the group consisting of a pl6INK4a/CDKN2A transcriptional promoter and a p21/CDKNlA transcriptional promoter.

11. The expression construct of claim 9 wherein said transcriptional promoter is responsive to a factor selected from the group consisting of SP1, ETS1, ETS2, and p53/TP53.

12. The expression construct of claim 9 wherein said nucleic acid encodes a therapeutic protein selected from the group consisting of CASP3, CASP8, CASP9, BAX, DFF40, HSV-TK, and cytosine deaminase.

13. The expression construct of claim 9 wherein said therapeutic protein induces cell death in said target cell.

14. The expression construct of claim 13 wherein said induced cell death occurs via a cellular process selected from the group consisting of apoptosis, necrosis/necroptosis, autophagic cell death, endoplasmic reticulum-stress associated cytotoxicity, mitotic catastrophe, paraptosis, pyroptosis, pyronecrosis, and entosifs.

15. The expression construct of claim 8 wherein said human mammalian target cell is a cancer cell.

16. The expression construct of claim 13 wherein said cancer cell is selected from the group consisting of a brain cancer cell, a prostate cancer cell, a lung cancer cell, a colorectal cancer cell, a breast cancer cell, a liver cancer cell, a hematologic cancer cell, and a bone cancer cell.

17. The expression construct of claim 13 wherein said transcriptional promoter is selected from the group consisting of the p21clP1/wafl promoter, the p27kipl promoter, the p57kip2 promoter, the TdT promoter, the Rag-1 promoter, the B29 promoter, the Blk promoter, the CD 19 promoter, the BLNK promoter, and the l5 promoter.

18. The expression construct of claim 13 wherein said transcriptional promoter is responsive to a factor selected from the group consisting of an EBF3, O/E-1, Pax-5, E2A,p53, VP16, MLL, HSF1, NF-IL6, NFAT1, AP-1, AP-2, HOX, E2F3, and/or NF-KB transcription factor.

19. The expression construct of claim 13 wherein said nucleic acid encodes a therapeutic protein selected from the group consisting of CASP3, CASP8, CASP9, BAX, DFF40, HSV-TK, and cytosine deaminase.

20. The expression construct of claim 8 wherein said target cell is a human cell that is infected with an infectious disease agent or a bacterial cell.

21. The expression construct of claim 20 wherein said infectious agent is a virus selected from the group consisting of a herpes virus, a polio virus, a hepatitis virus, a retrovirus virus, an influenza virus, and a rhino virus.

22. The expression construct of claim 20 wherein said nucleic acid encodes a therapeutic protein selected from the group consisting of CASP3, CASP8, CASP9, BAX, DFF40, HSV-TK, and cytosine deaminase.

23. A system for the targeted production of a therapeutic protein within a target cell, said system comprising:

a. a vector that is capable of delivering a nucleic acid to a cell, said vector comprising an expression construct; and

b. an expression construct for the targeted production of a therapeutic protein within a target cell, said expression construct comprising:

i. a transcriptional promoter that is activated in response to one or more factors each of which is produced within said target cell; and

ii. a nucleic acid that is operably linked to and under regulatory control of said transcriptional promoter, wherein said nucleic acid encodes a therapeutic protein that can reduce, prevent, and/or eliminate the growth and/or survival of a cell, including said target cell.

24. The system of claim 23 wherein said vector is selected from the group consisting of a liposome, a viral vector, a nanoparticle, a polyplex, and a dendrimer.

25. The system of claim 23 wherein said vector is a liposome wherein said liposome comprises a fusogenic peptide

26. The system of claim 23 wherein said vector is a viral vector wherein said viral vector comprises is selected from the group consisting of a herpes simplex viral vector, a lentiviral vector, an adenoviral vetor, and an adeno-associated viral vector.

27. The system of claim 23 wherein said vector is a nanoparticle wherein said nanoparticle is selected from the group consisting of a including a gold nanoparticle, a silica nanoparticle, an iron oxide nanoparticle, a titanium nanoparticle, a hydrogel nanoparticle, and a calcium phosphate nanoparticle.

28. The system of claim 23 wherein said transcriptional promoter is activated in said target cell but is not activated in a normal mammalian cell that is not associated with said disease.

29. The system of claim 23 wherein at least one of said factors is not produced in said normal mammalian cell that is not associated with said disease.

30. The system of claim 23 wherein said mammalian target cell is a human cell selected from the group consisting of a senescent cell, a cancer cell, and a cell that is infected with an infectious disease agent.

31. The system of claim 30 wherein said human target cell is a senescent cell.

32. The system of claim 30 wherein said transcriptional promoter is selected from the group consisting of a pl6INK4a/CDKN2A transcriptional promoter and a p21/CDKNlA transcriptional promoter.

33. The system of claim 32 wherein said transcriptional promoter is responsive to a factor selected from the group consisting of SP1, ETS1, ETS2, and p53/TP53.

34. The system of claim 30 wherein said nucleic acid encodes a therapeutic protein selected from the group consisting of CASP3, CASP8, CASP9, BAX, DFF40, HSV-TK, and cytosine deaminase.

35. The system of claim 34 wherein said therapeutic protein induces cell death in said target cell.

36. The system of claim 35 wherein said induced cell death occurs via a cellular process selected from the group consisting of apoptosis, necrosis/necroptosis, autophagic cell death, endoplasmic reticulum-stress associated cytotoxicity, mitotic catastrophe, paraptosis, pyroptosis, pyronecrosis, and entosifs.

37. The system of claim 30 wherein said human mammalian target cell is a cancer cell.

38. The system of claim 37 wherein said cancer cell is selected from the group consisting of a brain cancer cell, a prostate cancer cell, a lung cancer cell, a colorectal cancer cell, a breast cancer cell, a liver cancer cell, a hematologic cancer cell, and a bone cancer cell.

39. The system of claim 37 wherein said transcriptional promoter is selected from the group consisting of the p21c P^wa^ promoter, the p27^'P ' promoter, the p57^'P^ promoter, the TdT promoter, the Rag-1 promoter, the B29 promoter, the Blk promoter, the CD 19 promoter, the BLNK promoter, and the l5 promoter.

40. The system of claim 37 wherein said transcriptional promoter is responsive to a factor selected from the group consisting of EBF3, O/E-1, Pax-5, E2A, p53, VP16, MLL, HSF1, NF-IL6, NFAT1, and NF-kB.

41. The system of claim 37 wherein said nucleic acid encodes a therapeutic protein selected from the group consisting of CASP3, CASP8, CASP9, BAX, DFF40, HSV-TK, and cytosine deaminase.

42. The system of claim 30 wherein said target cell is a human cell that is infected with an infectious disease agent.

43. The system of claim 42 wherein said infectious agent is a virus selected from the group consisting of a herpes virus, a polio virus, a hepatitis virus, a retrovirus virus, an influenza virus, and a rhino virus.

44. The system of claim 42 wherein said nucleic acid encodes a therapeutic protein selected from the group consisting of CASP3, CASP8, CASP9, BAX, DFF40, HSV-TK, and cytosine deaminase.

45. A method for reducing, preventing, and/or eliminating the growth of a target cell, said method comprising contacting a target cell with a system for the targeted production of a therapeutic protein within said target cell, said system comprising:

a. a vector that is capable of delivering a nucleic acid to a cell, said vector comprising an expression construct; and

b. an expression construct for the targeted production of a therapeutic protein within a target cell, said expression construct comprising (i) a transcriptional promoter that is activated in response to one or more factors each of which is produced within said target cell; and (ii) a nucleic acid that is operably linked to and under regulatory control of said transcriptional promoter, wherein said nucleic acid encodes a therapeutic protein,

wherein production of said therapeutic protein in said target cell reduces, prevents, and/or eliminates the growth and/or survival of said target cell.

46. A method for the treatment of a disease or condition in a patient having a target cell, said method comprising: administering to said patient a system for the targeted production of a therapeutic protein within a target cell, said system comprising

a. a vector that is capable of delivering a nucleic acid to a cell, said vector comprising an expression construct; and

b. an expression construct for the targeted production of a therapeutic protein within a target cell, said expression construct comprising (i) a transcriptional promoter that is activated in response to one or more factors each of which is produced within said target cell; and (ii) a nucleic acid that is operably linked to and under regulatory control of said transcriptional promoter, wherein said nucleic acid encodes a therapeutic protein, wherein production of said therapeutic protein in said target cell reduces, prevents, and/or eliminates the growth and/or survival of said target cell thereby slowing, reversing, and/or eliminating said disease or condition in said patient.