Compositions, constructs, and vectors for cell reprogramming

JP7874329B2Active Publication Date: 2026-06-16ASGARD THERAPEUTICS AB
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Patent Information

Authority / Receiving Office
JP · JP
Patent Type
Patents
Current Assignee / Owner
ASGARD THERAPEUTICS AB
Filing Date
2021-12-17
Publication Date
2026-06-16

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Abstract

The present disclosure relates to compositions, vectors, constructs, cells and methods for reprogramming cells into natural killer (NK) cells or progenitor cells. In particular, the present disclosure relates to combinations of transcription factors for the reprogramming of cells.
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Claims

1. One or more constructs or vectors comprising at least one polynucleotide, wherein the one or more constructs or vectors encode a combination of at least three different transcription factors selected from the group consisting of ETS1, TBET, NFIL3, and EOMES.

2. The at least one polynucleotide is a. The transcription factor ETS1 and / or comprising the amino acid sequence of SEQ ID NO: 1, or a variant that shares at least 90% sequence identity with the amino acid sequence of SEQ ID NO: 1 and has the same transcriptional activity as the transcription factor consisting of the amino acid sequence of SEQ ID NO:

1. b. The transcription factor TBET and / or comprising the amino acid sequence of SEQ ID NO: 2, or a variant that shares at least 90% sequence identity with the amino acid sequence of SEQ ID NO: 2 and has the same transcriptional activity as the transcription factor comprising the amino acid sequence of SEQ ID NO:

2. c. The transcription factor NFIL3 and / or comprising the amino acid sequence of SEQ ID NO: 3, or a variant that shares at least 90% sequence identity with the amino acid sequence of SEQ ID NO: 3 and has the same transcriptional activity as the transcription factor consisting of the amino acid sequence of SEQ ID NO:

3. d. The transcription factor EOMES comprising the amino acid sequence of SEQ ID NO: 4, 5, or 6, or a variant that shares at least 90% sequence identity with the amino acid sequence of SEQ ID NO: 4, 5, or 6, and has the same transcriptional activity as the transcription factor consisting of the amino acid sequence of SEQ ID NO: 4, 5, or 6. A construct or vector according to claim 1, which codes for the following.

3. a. The polynucleotide encoding SEQ ID NO: 1 is a sequence having at least 90% sequence identity with SEQ ID NO: 22, or the sequence of SEQ ID NO: 22, and / or b. The polynucleotide encoding Sequence ID 2 is a sequence having at least 90% sequence identity with Sequence ID 23, or the sequence of Sequence ID 23, and / or c. The polynucleotide encoding Sequence ID 3 is a sequence having at least 90% sequence identity with Sequence ID 24, or the sequence of Sequence ID 24, and / or d. The polynucleotides encoding sequence numbers 4 to 6 are selected from the group consisting of sequences having at least 90% sequence identity with sequence numbers 25, 26, and 27, or sequence numbers 25, 26, and 27. The structure or vector according to claim 2.

4. The at least one polynucleotide is ETS1, TBET, NFIL3 and EOMES, ETS1, TBET and NFIL3, ETS1, TBET and EOMES, ETS1, NFIL3 and EOMES, A construct or vector according to any one of claims 1 to 3, encoding a combination of at least three transcription factors selected from the group consisting of TBET, NFIL3, and EOMES.

5. The construct or vector according to any one of claims 1 to 4, wherein the at least one polynucleotide further encodes one or more transcription factors selected from the group consisting of ID2, GATA3, ZFP105, IKZF3, TOX, RUNX3, KLF12, ZEB2, IRF2, STAT5, IKZF1, ELF4, ZBTB16, GATA2, and ELF1.

6. The construct or vector according to any one of claims 1 to 5, wherein the vector is a viral vector.

7. The construct or vector according to claim 6, wherein the vector is selected from the group consisting of lentivirus vectors, retrovirus vectors, adenovirus vectors, herpesvirus vectors, poxvirus vectors, flavivirus vectors, rhabdovirus vectors, paramyxovirus vectors, adeno-associated virus vectors, reovirus vectors, papillomavirus vectors, picornavirus vectors, calicivirus vectors, hepadnavirus vectors, togavirus vectors, coronavirus vectors, hepatitis virus vectors, orthomyxovirus vectors, bunyavirus vectors, and filovirus vectors.

8. The construct or vector according to claim 6 or 7, wherein the vector is a tumor-lytic vector.

9. The construct or vector according to any one of claims 1 to 8, wherein the construct or vector is synthetic mRNA, a naked alphavirus RNA replicon, or a naked flavivirus RNA replicon.

10. The construct or vector according to any one of claims 1 to 9, wherein the vector further comprises a promoter sequence that controls the transcription of at least one polynucleotide according to any one of claims 1 to 5.

11. The construct or vector according to claim 10, wherein the promoter sequence is selected from the group consisting of the splenic lesion-forming virus (SFFV) promoter, the cytomegalovirus (CMV) promoter, the phosphoglycerate kinase (PGK) promoter, the myelin basic protein (MBP) promoter, the glial fibrillary acidic protein (GFAP) promoter, the modified MoMuLV LTR containing the myeloproliferative sarcoma virus enhancer (MNDU3), the ubiquitin C promoter, the EF-1α promoter, or the mouse stem cell virus (MSCV) promoter.

12. The construct or vector according to any one of claims 1 to 11, wherein the construct or vector is a plasmid.

13. The construct or vector according to any one of claims 1 to 12, wherein the construct or vector is a CRISPR / CAS activation system.

14. A cell comprising the construct or vector according to any one of claims 1 to 13.

15. The cells according to claim 14, wherein the cells are selected from the group consisting of stem cells, differentiated cells, cancer cells, or tumor cells.

16. The cells according to claim 15, wherein the stem cells are selected from the group consisting of pluripotent stem cells and multipotent stem cells such as mesenchymal stem cells, and hematopoietic stem cells.

17. A pharmaceutical composition comprising a construct or vector according to any one of claims 1 to 13, and / or cells according to any one of claims 14 to 16.

18. A method for reprogramming or inducing cells into natural killer cells or progenitor cells, the method comprising the following steps: a. Transducing cells using a construct or vector according to any one of claims 1 to 13, or a pharmaceutical composition according to claim 17, b. A step of culturing and growing transduced cells in a cell medium, c. Steps to obtain reprogrammed cells Methods that include...

19. Induced natural killer cells or progenitor cells obtained by the method described in claim 18.

20. A construct or vector according to any one of claims 1 to 13, a cell according to any one of claims 14 to 16, a pharmaceutical composition according to claim 17, and / or an induced natural killer cell or progenitor cell according to claim 19, for use in medical applications.

21. A construct or vector according to any one of claims 1 to 13, a cell according to any one of claims 14 to 16, a pharmaceutical composition according to claim 17, and / or an induced natural killer cell or progenitor cell according to claim 19, for use in cancer treatment.

22. A construct or vector according to any one of claims 1 to 13, a cell according to any one of claims 14 to 16, a pharmaceutical composition according to claim 17, and / or an induced natural killer cell or progenitor cell according to claim 19, for use in immunotherapy.