Novel artificial nucleic acid molecules

JP2026090405APending Publication Date: 2026-06-02CUREVAC SE
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Patent Information

Authority / Receiving Office
JP · JP
Patent Type
Applications
Current Assignee / Owner
CUREVAC SE
Filing Date
2026-02-12
Publication Date
2026-06-02

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Abstract

This invention provides artificial nucleic acid molecules that enhance the efficacy of therapeutic nucleic acids. [Solution] The present invention provides an artificial nucleic acid molecule comprising a novel combination of 5' and 3' untranslated region (UTR) factors. The nucleic acid molecule of the present invention is preferably characterized by increased expression efficiency of a coding region operably linked to the UTR factors. The artificial nucleic acid can be used for the treatment or prevention of various diseases. The present invention further provides (pharmaceutical) compositions, vaccines, and kits comprising the artificial nucleic acid molecule. Furthermore, an in vitro method for preparing the artificial nucleic acid molecule of the present invention is provided.
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Claims

1. a. A 5'-UTR factor derived from the 5' untranslated region (5'-UTR) of the HSD17B4 gene and a 3'-UTR factor derived from the 3' untranslated region (3'-UTR) of the GNAS gene; and at least one coding region operably linked to the 5'-UTR factor and the 3'-UTR factor; or b. A 5'-UTR factor derived from the 5' untranslated region (5'-UTR) of the NDUFA4 gene and a 3'-UTR factor derived from the 3' untranslated region (3'-UTR) of the CASP1 gene; and at least one coding region operably linked to the 5'-UTR factor and the 3'-UTR factor; or c. 5'-UTR factors derived from the 5' untranslated region (5'-UTR) of genes selected from the group consisting of HSD17B4, ASAH1, ATP5A1, MP68, NDUFA4, NOSIP, RPL31, SLC7A3, TUBB4B, and UBQLN2; and, 3'-UTR factors derived from the 3' untranslated region (3'-UTR) of genes selected from the group consisting of PSMB3, CASP1, COX6B1, GNAS, NDUFA1, and RPS9; and, At least one coding region operably connected to the 5'-UTR and the 3'-UTR, An artificial nucleic acid molecule comprising, The coding region described above is an artificial nucleic acid molecule that does not encode CRISPR-related proteins.

2. The artificial nucleic acid molecule according to claim 1, wherein the 5'-UTR factor and / or the 3'-UTR factor are heterogeneous with respect to the coding region.

3. Each of the above UTRs comprises a naturally occurring DNA sequence and its homologs, variants, fragments, and corresponding RNA sequences, according to claim 1 or 2, an artificial nucleic acid molecule.

4. f-4: At least one 5'-UTR factor derived from the 5'-UTR of the HSD17B4 gene, or its corresponding RNA sequence, homolog, fragment, or variant, and at least one 3'-UTR factor derived from the 3'-UTR of the GNAS1 gene, or its corresponding RNA sequence, homolog, fragment, or variant; or g-2: At least one 5'-UTR factor derived from the 5'-UTR of the NDUFA4 gene, or its corresponding RNA sequence, homolog, fragment, or variant, and at least one 3'-UTR factor derived from the 3'-UTR of the CASP1 gene, or its corresponding RNA sequence, homolog, fragment, or variant; or a-1: At least one 5'-UTR factor derived from the 5'-UTR of the HSD17B4 gene, or its corresponding RNA sequence, homolog, fragment, or variant, and at least one 3'-UTR factor derived from the 3'-UTR of the PSMB3 gene, or its corresponding RNA sequence, homolog, fragment, or variant; or a-2: At least one 5'-UTR factor derived from the 5'-UTR of the NDUFA4 gene, or its corresponding RNA sequence, homolog, fragment, or variant, and at least one 3'-UTR factor derived from the 3'-UTR of the PSMB3 gene, or its corresponding RNA sequence, homolog, fragment, or variant; or a-3: At least one 5'-UTR factor derived from the 5'-UTR of the SLC7A3 gene, or its corresponding RNA sequence, homolog, fragment, or variant, and at least one 3'-UTR factor derived from the 3'-UTR of the PSMB3 gene, or its corresponding RNA sequence, homolog, fragment, or variant; or a-4: At least one 5'-UTR factor derived from the 5'-UTR of the NOSIP gene, or its corresponding RNA sequence, homolog, fragment, or variant, and at least one 3'-UTR factor derived from the 3'-UTR of the PSMB3 gene, or its corresponding RNA sequence, homolog, fragment, or variant; or a-5: At least one 5'-UTR factor derived from the 5'-UTR of the MP68 gene, or its corresponding RNA sequence, homolog, fragment, or variant, and at least one 3'-UTR factor derived from the 3'-UTR of the PSMB3 gene, or its corresponding RNA sequence, homolog, fragment, or variant; or b-1: At least one 5'-UTR factor derived from the 5'-UTR of the UBQLN2 gene, or its corresponding RNA sequence, homolog, fragment, or variant, and at least one 3'-UTR factor derived from the 3'-UTR of the RPS9 gene, or its corresponding RNA sequence, homolog, fragment, or variant; or b-2: At least one 5'-UTR factor derived from the 5'-UTR of the ASAH1 gene, or its corresponding RNA sequence, homolog, fragment, or variant, and at least one 3'-UTR factor derived from the 3'-UTR of the RPS9 gene, or its corresponding RNA sequence, homolog, fragment, or variant; or b-3: At least one 5'-UTR factor derived from the 5'-UTR of the HSD17B4 gene, or its corresponding RNA sequence, homolog, fragment, or variant, and at least one 3'-UTR factor derived from the 3'-UTR of the RPS9 gene, or its corresponding RNA sequence, homolog, fragment, or variant; or b-4: At least one 5'-UTR factor derived from the 5'-UTR of the HSD17B4 gene, or its corresponding RNA sequence, homolog, fragment, or variant, and at least one 3'-UTR factor derived from the 3'-UTR of the CASP1 gene, or its corresponding RNA sequence, homolog, fragment, or variant; or b-5: At least one 5'-UTR factor derived from the 5'-UTR of the NOSIP gene, or its corresponding RNA sequence, homolog, fragment, or variant, and at least one 3'-UTR factor derived from the 3'-UTR of the COX6B1 gene, or its corresponding RNA sequence, homolog, fragment, or variant; or c-1: At least one 5'-UTR factor derived from the 5'-UTR of the NDUFA4 gene, or its corresponding RNA sequence, homolog, fragment, or variant, and at least one 3'-UTR factor derived from the 3'-UTR of the RPS9 gene, or its corresponding RNA sequence, homolog, fragment, or variant; or c-2: At least one 5'-UTR factor derived from the 5'-UTR of the NOSIP gene, or its corresponding RNA sequence, homolog, fragment, or variant, and at least one 3'-UTR factor derived from the 3'-UTR of the NDUFA1 gene, or its corresponding RNA sequence, homolog, fragment, or variant; or c-3: At least one 5'-UTR factor derived from the 5'-UTR of the NDUFA4 gene, or its corresponding RNA sequence, homolog, fragment, or variant, and at least one 3'-UTR factor derived from the 3'-UTR of the COX6B1 gene, or its corresponding RNA sequence, homolog, fragment, or variant; or c-4: At least one 5'-UTR factor derived from the 5'-UTR of the NDUFA4 gene, or its corresponding RNA sequence, homolog, fragment, or variant, and at least one 3'-UTR factor derived from the 3'-UTR of the NDUFA1 gene, or its corresponding RNA sequence, homolog, fragment, or variant; or c-5: At least one 5'-UTR factor derived from the 5'-UTR of the ATP5A1 gene, or its corresponding RNA sequence, homolog, fragment, or variant, and at least one 3'-UTR factor derived from the 3'-UTR of the PSMB3 gene, or its corresponding RNA sequence, homolog, fragment, or variant; or d-1: At least one 5'-UTR factor derived from the 5'-UTR of the RPL31 gene, or its corresponding RNA sequence, homolog, fragment, or variant, and at least one 3'-UTR factor derived from the 3'-UTR of the PSMB3 gene, or its corresponding RNA sequence, homolog, fragment, or variant; or d-2: At least one 5'-UTR factor derived from the 5'-UTR of the ATP5A1 gene, or its corresponding RNA sequence, homolog, fragment, or variant, and at least one 3'-UTR factor derived from the 3'-UTR of the CASP1 gene, or its corresponding RNA sequence, homolog, fragment, or variant; or d-3: At least one 5'-UTR factor derived from the 5'-UTR of the SLC7A3 gene, or its corresponding RNA sequence, homolog, fragment, or variant, and at least one 3'-UTR factor derived from the 3'-UTR of the GNAS1 gene, or its corresponding RNA sequence, homolog, fragment, or variant; or d-4: At least one 5'-UTR factor derived from the 5'-UTR of the HSD17B4 gene, or its corresponding RNA sequence, homolog, fragment, or variant, and at least one 3'-UTR factor derived from the 3'-UTR of the NDUFA1 gene, or its corresponding RNA sequence, homolog, fragment, or variant; or d-5: At least one 5'-UTR factor derived from the 5'-UTR of the SLC7A3 gene, or its corresponding RNA sequence, homolog, fragment, or variant, and at least one 3'-UTR factor derived from the 3'-UTR of the NDUFA1 gene, or its corresponding RNA sequence, homolog, fragment, or variant; or e-1: At least one 5'-UTR factor derived from the 5'-UTR of the TUBB4B gene, or its corresponding RNA sequence, homolog, fragment, or variant, and at least one 3'-UTR factor derived from the 3'-UTR of the RPS9 gene, or its corresponding RNA sequence, homolog, fragment, or variant; or e-2: At least one 5'-UTR factor derived from the 5'-UTR of the RPL31 gene, or its corresponding RNA sequence, homolog, fragment, or variant, and at least one 3'-UTR factor derived from the 3'-UTR of the RPS9 gene, or its corresponding RNA sequence, homolog, fragment, or variant; or e-3: At least one 5'-UTR factor derived from the 5'-UTR of the MP68 gene, or its corresponding RNA sequence, homolog, fragment, or variant, and at least one 3'-UTR factor derived from the 3'-UTR of the RPS9 gene, or its corresponding RNA sequence, homolog, fragment, or variant; or e-4: At least one 5'-UTR factor derived from the 5'-UTR of the NOSIP gene, or its corresponding RNA sequence, homolog, fragment, or variant, and at least one 3'-UTR factor derived from the 3'-UTR of the RPS9 gene, or its corresponding RNA sequence, homolog, fragment, or variant; or e-5: At least one 5'-UTR factor derived from the 5'-UTR of the ATP5A1 gene, or its corresponding RNA sequence, homolog, fragment, or variant, and at least one 3'-UTR factor derived from the 3'-UTR of the RPS9 gene, or its corresponding RNA sequence, homolog, fragment, or variant; or e-6: At least one 5'-UTR factor derived from the 5'-UTR of the ATP5A1 gene, or its corresponding RNA sequence, homolog, fragment, or variant, and at least one 3'-UTR factor derived from the 3'-UTR of the COX6B1 gene, or its corresponding RNA sequence, homolog, fragment, or variant; or f-1: At least one 5'-UTR factor derived from the 5'-UTR of the ATP5A1 gene, or its corresponding RNA sequence, homolog, fragment, or variant, and at least one 3'-UTR factor derived from the 3'-UTR of the GNAS gene, or its corresponding RNA sequence, homolog, fragment, or variant; or f-2: At least one 5'-UTR factor derived from the 5'-UTR of the ATP5A1 gene, or its corresponding RNA sequence, homolog, fragment, or variant, and at least one 3'-UTR factor derived from the 3'-UTR of the NDUFA1 gene, or its corresponding RNA sequence, homolog, fragment, or variant; or f-3: At least one 5'-UTR factor derived from the 5'-UTR of the HSD17B4 gene, or its corresponding RNA sequence, homolog, fragment, or variant, and at least one 3'-UTR factor derived from the 3'-UTR of the COX6B1 gene, or its corresponding RNA sequence, homolog, fragment, or variant; or f-5: At least one 5'-UTR factor derived from the 5'-UTR of the MP68 gene, or its corresponding RNA sequence, homolog, fragment, or variant, and at least one 3'-UTR factor derived from the 3'-UTR of the COX6B1 gene, or its corresponding RNA sequence, homolog, fragment, or variant; or g-1: At least one 5'-UTR factor derived from the 5'-UTR of the MP68 gene, or its corresponding RNA sequence, homolog, fragment, or variant, and at least one 3'-UTR factor derived from the 3'-UTR of the NDUFA1 gene, or its corresponding RNA sequence, homolog, fragment, or variant; or g-3: At least one 5'-UTR factor derived from the 5'-UTR of the NDUFA4 gene, or its corresponding RNA sequence, homolog, fragment, or variant, and at least one 3'-UTR factor derived from the 3'-UTR of the GNAS gene, or its corresponding RNA sequence, homolog, fragment, or variant; or g-4: At least one 5'-UTR factor derived from the 5'-UTR of the NOSIP gene, or its corresponding RNA sequence, homolog, fragment, or variant, and at least one 3'-UTR factor derived from the 3'-UTR of the CASP1 gene, or its corresponding RNA sequence, homolog, fragment, or variant; or g-5: At least one 5'-UTR factor derived from the 5'-UTR of the RPL31 gene, or its corresponding RNA sequence, homolog, fragment, or variant, and at least one 3'-UTR factor derived from the 3'-UTR of the CASP1 gene, or its corresponding RNA sequence, homolog, fragment, or variant; or h-1: At least one 5'-UTR factor derived from the 5'-UTR of the RPL31 gene, or its corresponding RNA sequence, homolog, fragment, or variant, and at least one 3'-UTR factor derived from the 3'-UTR of the COX6B1 gene, or its corresponding RNA sequence, homolog, fragment, or variant; or h-2: At least one 5'-UTR factor derived from the 5'-UTR of the RPL31 gene, or its corresponding RNA sequence, homolog, fragment, or variant, and at least one 3'-UTR factor derived from the 3'-UTR of the GNAS gene, or its corresponding RNA sequence, homolog, fragment, or variant; or h-3: At least one 5'-UTR factor derived from the 5'-UTR of the RPL31 gene, or its corresponding RNA sequence, homolog, fragment, or variant, and at least one 3'-UTR factor derived from the 3'-UTR of the NDUFA1 gene, or its corresponding RNA sequence, homolog, fragment, or variant; or h-4: At least one 5'-UTR factor derived from the 5'-UTR of the SLC7A3 gene, or its corresponding RNA sequence, homolog, fragment, or variant, and at least one 3'-UTR factor derived from the 3'-UTR of the CASP1 gene, or its corresponding RNA sequence, homolog, fragment, or variant; or h-5: At least one 5'-UTR factor derived from the 5'-UTR of the SLC7A3 gene, or its corresponding RNA sequence, homolog, fragment, or variant, and at least one 3'-UTR factor derived from the 3'-UTR of the COX6B1 gene, or its corresponding RNA sequence, homolog, fragment, or variant; or i-1: At least one 5'-UTR factor derived from the 5'-UTR of the SLC7A3 gene, or its corresponding RNA sequence, homolog, fragment, or variant, and at least one 3'-UTR factor derived from the 3'-UTR of the RPS9 gene, or its corresponding RNA sequence, homolog, fragment, or variant; or i-2: At least one 5'-UTR factor derived from the 5'-UTR of the Ndufa4.1 gene, or its corresponding RNA sequence, homolog, fragment, or variant, and at least one 3'-UTR factor derived from the 3'-UTR of the CASP1 gene, or its corresponding RNA sequence, homolog, fragment, or variant, An artificial nucleic acid molecule according to any one of claims 1 to 3, comprising:

5. The artificial nucleic acid molecule according to claim 4, comprising the UTR factor described in f-4, g-2, a-1, a-2, a-3, a-4, or a-5, preferably f-4 or g-2.

6. - The 5'-UTR factor derived from the HSD17B4 gene contains or comprises a DNA sequence, fragment or variant thereof having at least 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% (higher is preferable) sequence identity with the DNA sequence described in SEQ ID NO: 1, or the nucleic acid sequence described in SEQ ID NO: 1, or contains or comprises an RNA sequence, fragment or variant thereof having at least 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% (higher is preferable) sequence identity with the RNA sequence described in SEQ ID NO: 2, or the nucleic acid sequence described in SEQ ID NO: 2, - The 5'-UTR factor derived from the above NDUFA4 gene contains or comprises a DNA sequence, fragment or variant thereof having at least 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% (higher is preferable) sequence identity with the DNA sequence described in SEQ ID NO: 9, or the nucleic acid sequence described in SEQ ID NO: 9, or contains or comprises an RNA sequence, fragment or variant thereof having at least 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% (higher is preferable) sequence identity with the RNA sequence described in SEQ ID NO: 10, or the nucleic acid sequence described in SEQ ID NO:

10. - The 5'-UTR factor derived from the ASAH1 gene described above contains or comprises a DNA sequence, fragment or variant thereof having at least 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% (higher is preferable) sequence identity with the DNA sequence described in SEQ ID NO: 3, or the nucleic acid sequence described in SEQ ID NO: 3, or contains or comprises an RNA sequence, fragment or variant thereof having at least 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% (higher is preferable) sequence identity with the RNA sequence described in SEQ ID NO: 4, or the nucleic acid sequence described in SEQ ID NO:

4. - The 5'-UTR factor derived from the ATP5A1 gene contains or comprises a DNA sequence, fragment or variant thereof having at least 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% (higher is preferable) sequence identity with the DNA sequence described in Sequence ID No. 5, or the nucleic acid sequence described in Sequence ID No. 5, or contains or comprises an RNA sequence, fragment or variant thereof having at least 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% (higher is preferable) sequence identity with the RNA sequence described in Sequence ID No. 6, or the nucleic acid sequence described in Sequence ID No.

6. - The 5'-UTR factor derived from the MP68 gene contains or comprises a DNA sequence, fragment or variant thereof having at least 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% (higher is preferable) sequence identity with the DNA sequence described in Sequence ID No. 7, or the nucleic acid sequence described in Sequence ID No. 7, or contains or comprises an RNA sequence, fragment or variant thereof having at least 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% (higher is preferable) sequence identity with the RNA sequence described in Sequence ID No. 8, or the nucleic acid sequence described in Sequence ID No.

8. - The 5'-UTR factor derived from the above NOSIP gene contains or comprises a DNA sequence, fragment or variant thereof having at least 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% (higher is preferable) sequence identity with the DNA sequence described in SEQ ID NO: 11, or the nucleic acid sequence described in SEQ ID NO: 11, or contains or comprises an RNA sequence, fragment or variant thereof having at least 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% (higher is preferable) sequence identity with the RNA sequence described in SEQ ID NO: 12, or the nucleic acid sequence described in SEQ ID NO:

12. - The 5'-UTR factor derived from the RPL31 gene contains or comprises a DNA sequence, fragment or variant thereof having at least 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% (higher is preferable) sequence identity with the DNA sequence described in SEQ ID NO: 13, or the nucleic acid sequence described in SEQ ID NO: 13, or contains or comprises an RNA sequence, fragment or variant thereof having at least 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% (higher is preferable) sequence identity with the RNA sequence described in SEQ ID NO: 14, or the nucleic acid sequence described in SEQ ID NO:

14. - The 5'-UTR factor derived from the above SLC7A3 gene contains or comprises a DNA sequence, fragment or variant thereof having at least 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% (higher is preferable) sequence identity with the DNA sequence described in SEQ ID NO: 15, or the nucleic acid sequence described in SEQ ID NO: 15, or contains or comprises an RNA sequence, fragment or variant thereof having at least 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% (higher is preferable) sequence identity with the RNA sequence described in SEQ ID NO: 16, or the nucleic acid sequence described in SEQ ID NO:

16. - The 5'-UTR factor derived from the TUBB4B gene described above contains or comprises a DNA sequence, fragment or variant thereof having at least 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% (higher is preferable) sequence identity with the DNA sequence described in SEQ ID NO: 17, or the nucleic acid sequence described in SEQ ID NO: 17, or contains or comprises an RNA sequence, fragment or variant thereof having at least 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% (higher is preferable) sequence identity with the RNA sequence described in SEQ ID NO: 18, or the nucleic acid sequence described in SEQ ID NO:

18. - The 5'-UTR factor derived from the UBQLN2 gene described above contains or comprises a DNA sequence, fragment or variant thereof having at least 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% (higher is preferable) sequence identity with the DNA sequence described in SEQ ID NO: 19, or the nucleic acid sequence described in SEQ ID NO: 19, or contains or comprises an RNA sequence, fragment or variant thereof having at least 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% (higher is preferable) sequence identity with the RNA sequence described in SEQ ID NO: 20, or the nucleic acid sequence described in SEQ ID NO:

20. - The 3'-UTR factor derived from the above GNAS gene contains or comprises a DNA sequence, fragment or variant thereof having at least 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% (higher is preferable) sequence identity with the DNA sequence described in SEQ ID NO: 29, or the nucleic acid sequence described in SEQ ID NO: 29, or contains or comprises an RNA sequence, fragment or variant thereof having at least 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% (higher is preferable) sequence identity with the RNA sequence described in SEQ ID NO: 30, or the nucleic acid sequence described in SEQ ID NO:

30. - The 3'-UTR factor derived from the CASP1 gene described above contains or comprises a DNA sequence, fragment or variant thereof having at least 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% (higher is preferable) sequence identity with the DNA sequence described in SEQ ID NO: 25, or the nucleic acid sequence described in SEQ ID NO: 25, or contains or comprises an RNA sequence, fragment or variant thereof having at least 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% (higher is preferable) sequence identity with the RNA sequence described in SEQ ID NO: 26, or the nucleic acid sequence described in SEQ ID NO:

26. - The 3'-UTR factor derived from the PSMB3 gene contains or comprises a DNA sequence, fragment or variant thereof having at least 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% (higher is preferable) sequence identity with the DNA sequence described in SEQ ID NO: 23, or the nucleic acid sequence described in SEQ ID NO: 23, or contains or comprises an RNA sequence, fragment or variant thereof having at least 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% (higher is preferable) sequence identity with the RNA sequence described in SEQ ID NO: 24, or the nucleic acid sequence described in SEQ ID NO:

24. - The 3'-UTR factor derived from the COX6B1 gene described above contains or comprises a DNA sequence, fragment or variant thereof having at least 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% (higher is preferable) sequence identity with the DNA sequence described in SEQ ID NO: 27, or the nucleic acid sequence described in SEQ ID NO: 27, or contains or comprises an RNA sequence, fragment or variant thereof having at least 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% (higher is preferable) sequence identity with the RNA sequence described in SEQ ID NO: 28, or the nucleic acid sequence described in SEQ ID NO:

28. - The 3'-UTR factor derived from the above NDUFA1 gene contains or comprises a DNA sequence, fragment or variant thereof having at least 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% (higher is preferable) sequence identity with the DNA sequence described in SEQ ID NO: 31, or the nucleic acid sequence described in SEQ ID NO: 31, or contains or comprises an RNA sequence, fragment or variant thereof having at least 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% (higher is preferable) sequence identity with the RNA sequence described in SEQ ID NO: 32, or the nucleic acid sequence described in SEQ ID NO: 32, and / or - The 3'-UTR factor derived from the RPS9 gene contains or comprises a DNA sequence, fragment or variant thereof having at least 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% (higher is preferable) sequence identity with the DNA sequence described in SEQ ID NO: 33, or the nucleic acid sequence described in SEQ ID NO: 33, or contains or comprises an RNA sequence, fragment or variant thereof having at least 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% (higher is preferable) sequence identity with the RNA sequence described in SEQ ID NO: 34, or the nucleic acid sequence described in SEQ ID NO:

34. An artificial nucleic acid molecule according to any one of claims 1 to 5.

7. The artificial nucleic acid molecule according to any one of claims 1 to 6, wherein the coding region is located between the 5'-UTR factor and the 3'-UTR factor, and preferably downstream of the 5'-UTR factor and upstream of the 3'-UTR factor.

8. An artificial nucleic acid molecule according to any one of claims 1 to 7, wherein the at least one coding region encodes at least one (poly)peptide or protein of interest, optionally at least one (poly)peptide or protein of interest selected from antigenic (poly)peptide or protein, allergenic (poly)peptide or protein, therapeutic (poly)peptide or protein, antibody, or a fragment, variant, or derivative of the above-mentioned (poly)peptide or protein of interest.

9. The artificial nucleic acid molecule according to claim 8, wherein the at least one antigenic (poly)peptide or protein is selected from tumor antigens, pathogenic antigens, autoantigens, alloantigens, or allergenic antigens.

10. The artificial nucleic acid molecule according to claim 9, wherein the at least one pathogenic antigen is selected from bacterial, viral, fungal, or protozoan antigens.

11. The above therapeutic (poly)peptides or proteins are - Therapeutic (poly)peptides or proteins that replace deficient, defective, or mutated proteins; - Therapeutic (poly)peptides or proteins that are beneficial for treating hereditary or acquired diseases, infections, or neoplasms (e.g., cancer or tumor diseases); - Adjuvants or immunostimulant therapeutic (poly)peptides or proteins; - therapeutic antibodies; - Peptide hormones; - Gene editing agents; - Immune checkpoint inhibitors; - T cell receptor; -enzyme; and / or - A variant, fragment, or derivative of any of the above therapeutic (poly)peptides or proteins, An artificial nucleic acid molecule according to claim 8, selected from the above.

12. The above at least one coding area is further, (a) at least one effects domain; (b) at least one peptide or protein tag; (c) at least one localization signal or sequence; (d) at least one nuclear localization signal (NLS); (e) at least one signal peptide; and / or (f) at least one peptide linker; (g) Secretory signaling peptide (SSP), (h) Multimerizing factors including dimerizing factors, trimerizing factors, tetramerizing factors, or oligomerizing factors; (i) Factors that form virus-like particles (VLPs); (j) transmembrane factor; (k) Dendritic cell targeting factors; (l) Immunological adjuvant factors; (m) antigen presentation promoting factor; (n) 2A peptide; (o) Factors that prolong the half-life of proteins; and / or (p) Factors for post-translational modification (e.g., glycosylation), Code, The artificial nucleic acid molecule according to any one of claims 7 to 11, further comprising optionally at least one internal ribosome entry site (IRES) and / or at least one miRNA binding site.

13. An artificial nucleic acid molecule according to any one of claims 1 to 12, wherein the above-mentioned at least one coding region encodes an amino acid sequence having at least 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% (higher is preferable) sequence identity with respect to the amino acid sequence described in any one of SEQ ID NOs: 41 to 45, or a variant or fragment of any of these sequences, or comprising a (poly)peptide or protein.

14. The artificial nucleic acid molecule according to any one of claims 1 to 12, wherein the at least one coding region of the artificial nucleic acid molecule contains or consists of the nucleic acid sequence described in any one of sequence numbers 46 to 49; or contains or consists of a nucleic acid sequence having at least 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% (higher is preferable) sequence identity with respect to any one of the above nucleic acid sequences.

15. The artificial nucleic acid molecule according to any one of claims 1 to 13, comprising or consisting of a nucleic acid sequence described in any one of sequence numbers 50 to 368, or comprising or consisting of a nucleic acid sequence having at least 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% (higher is preferable) sequence identity with respect to any one of the above nucleic acid sequences.

16. The artificial nucleic acid molecule according to any one of claims 1 to 14, wherein the artificial nucleic acid molecule is RNA.

17. The RNA according to claim 16, wherein the RNA is monocistronic, bicistronic, or multicistronic.

18. The RNA according to claim 16 or 17, wherein the RNA is mRNA, viral RNA, self-replicating RNA, or replicon RNA.

19. The artificial nucleic acid is a modified nucleic acid, preferably a stabilized nucleic acid, or the artificial nucleic acid according to any one of claims 1 to 18, preferably RNA, comprising at least one modification or non-natural nucleotide, backbone modification, sugar modification, or base modification.

20. - The G / C content of the above-mentioned artificial nucleic acid is increased compared to the G / C content of the above-mentioned corresponding coding sequence of the above-mentioned wild-type artificial nucleic acid, and / or - The C content of the above-mentioned artificial nucleic acid is increased compared to the C content of the above-mentioned corresponding coding sequence of the above-mentioned wild-type artificial nucleic acid, and / or - The codon in the at least one coding region of the artificial nucleic acid is adapted to the frequency of use of human codons, and the codon adaptation index (CAI) is preferably increased or maximized in the at least one coding sequence of the artificial nucleic acid. - The amino acid sequence encoded by the above artificial nucleic acid is preferably unmodified compared to the amino acid sequence encoded by the corresponding wild-type artificial nucleic acid. An artificial nucleic acid, preferably RNA, according to any one of claims 1 to 19.

21. An artificial nucleic acid, preferably RNA, according to any one of claims 1 to 20, comprising a 5' cap structure, preferably m7GpppN or Cap1.

22. An artificial nucleic acid, preferably RNA, according to any one of claims 1 to 21, comprising at least one histone stem loop.

23. An artificial nucleic acid, preferably RNA, according to any one of claims 1 to 22, which optionally comprises a poly(A) sequence, preferably a poly(A) sequence containing 10 to 200, 10 to 100, 40 to 80, or 50 to 70 adenosine nucleotides.

24. An artificial nucleic acid, preferably RNA, according to any one of claims 1 to 23, optionally comprising a poly(C) sequence, preferably a poly(C) sequence containing 10 to 200, 10 to 100, 20 to 70, 20 to 60, or 10 to 40 cytosine nucleotides.

25. Preferably, in the direction from 5' to 3', the following factors: a) 5' cap structure, preferably m7GpppN or Cap1; b) A 5'-UTR factor comprising a nucleic acid sequence derived from a 5'-UTR as defined in any one of claims 1 to 6, or comprising said nucleic acid sequence, preferably a 5'-UTR factor comprising a nucleic acid sequence corresponding to the nucleic acid sequence described in SEQ ID NOs. 1 to 20 or its homolog, fragment, or variant. c) at least one coding sequence as defined in any one of claims 10 to 18; d) A 3'-UTR factor comprising a nucleic acid sequence derived from a 3'-UTR as defined in any one of claims 1 to 6, or comprising said nucleic acid sequence, preferably comprising a nucleic acid sequence corresponding to the nucleic acid sequence described in SEQ ID NOs. 23 to 34, or its homolog, fragment, or variant. e) Optionally, a poly(A) tail, preferably consisting of 10 to 1000, 10 to 500, 10 to 300, 10 to 200, 10 to 100, 40 to 80, or 50 to 70 adenosine nucleotides, f) Optionally, a poly(C) tail, preferably consisting of 10 to 200, 10 to 100, 20 to 70, 20 to 60 or 10 to 40 cytosine nucleotides, and g) Optionally, histone stem loop, An artificial nucleic acid, preferably RNA, according to any one of claims 1 to 24, comprising:

26. A composition comprising at least one artificial nucleic acid molecule, preferably RNA, according to any one of claims 1 to 25, and a pharmaceutically acceptable carrier and / or excipient.

27. The composition according to claim 26, which is used as a pharmaceutical and optionally as a vaccine.

28. The (pharmaceutical) composition according to claim 27, comprising at least one artificial nucleic acid molecule having the UTR combination described in claim 4, wherein the (pharmaceutical) composition and / or the artificial nucleic acid molecule is adapted for liver-targeted delivery, subcutaneous administration, intracutaneous administration, intradermal administration, topical administration, transdermal administration or intramuscular administration.

29. The (pharmaceutical) composition or vaccine according to any one of claims 25 to 28, wherein the above-mentioned artificial nucleic acid molecule, preferably RNA, forms a complex with one or more cationic or polycationic compounds and preferably a cationic or polycationic polymer, a cationic or polycationic peptide or protein, such as protamine, a cationic or polycationic polysaccharide, and / or a cationic or polycationic lipid, or a polymer carrier.

30. The (pharmaceutical) composition or vaccine according to claim 29, wherein the N / P ratio of the artificial nucleic acid molecule, preferably RNA, to one or more cationic or polycationic peptides or proteins is in the range of about 0.1 to 10, and includes the ranges of about 0.3 to 4, about 0.5 to 2, about 0.7 to 2, and about 0.7 to 1.

5.

31. The (pharmaceutical) composition or vaccine according to any one of claims 26 to 30, wherein the artificial nucleic acid molecule, preferably RNA, forms a complex with one or more lipids, thereby forming lipid nanoparticles, lipoplexes, and / or preferably liposomes.

32. A (pharmaceutical) composition or vaccine according to any one of claims 26 to 31, further comprising at least one further activator and / or at least one adjuvant.

33. A (pharmaceutical) composition or vaccine according to any one of claims 26 to 32, further comprising non-coding RNA selected from the group consisting of small interfering RNA (siRNA), antisense RNA (asRNA), circular RNA (circRNA), ribozymes, aptamers, riboswitches, immunostimulatory RNA (isRNA), transfer RNA (tRNA), ribosomal RNA (rRNA), nuclear small RNA (snRNA), nucleolar small RNA (snoRNA), microRNA (miRNA), and Piwi-binding RNA (piRNA).

34. A kit, preferably a kit of parts, comprising an artificial nucleic acid molecule according to any one of claims 1 to 25, preferably RNA, or a (pharmaceutical) composition or vaccine according to any one of claims 26 to 33, and optionally a liquid vehicle and / or optionally a technical instruction manual containing information on the use and dosage of the artificial nucleic acid molecule or the (pharmaceutical) composition or vaccine.

35. An artificial nucleic acid molecule according to any one of claims 1 to 25, preferably RNA, a (pharmaceutical) composition or vaccine according to any one of claims 26 to 33, or a kit according to claim 34, for use as a pharmaceutical.

36. An artificial nucleic acid molecule, preferably RNA, according to any one of claims 1 to 25, a (pharmaceutical) composition or vaccine according to any one of claims 26 to 33, or a kit according to claim 34, for use in the treatment of genetic diseases, cancer, infectious diseases, inflammatory diseases, (auto)immune diseases, allergies, and / or for use in gene therapy and / or immunomodulation.

37. The use described above comprises (a) administering the artificial nucleic acid molecule, preferably RNA, the (pharmaceutical) composition, or the kit to a patient in need of the use of the artificial nucleic acid molecule, preferably RNA, the (pharmaceutical) composition, or the vaccine or kit according to claim 36.

38. A (pharmaceutical) composition or vaccine according to any one of claims 26 to 33, or a kit according to claim 34, comprising at least one artificial nucleic acid molecule according to any one of claims 1 to 25, preferably RNA, or an artificial nucleic acid molecule according to any one of claims 4 to 25, for use in a method for increasing the expression efficiency of the above-mentioned artificial nucleic acid molecule in liver tissue, liver cells, liver cell lines, skin tissue, skin cells, skin cell lines, muscle tissue, muscle cells, or muscle cell lines.

39. Optionally, a method for treating or preventing a disease selected from genetic diseases, cancer, infectious diseases, inflammatory diseases, (auto)immune diseases, and allergies, and / or a method for use in gene therapy and / or immunomodulation, comprising administering an effective amount of an artificial nucleic acid molecule, preferably RNA, according to any one of claims 1 to 25, a (pharmaceutical) composition or vaccine according to any one of claims 26 to 33, or a kit according to claim 34, to a subject requiring such administration.