Engineered nucleic acids and methods of use thereof

1. A method comprising: administering to a subject in need thereof a pharmaceutical composition comprising:

i) a synthetic messenger ribonucleic acid (mRNA) encoding a G-CSF polypeptide; and

ii) a pharmaceutically acceptable carrier,

wherein the synthetic mRNA sequence is at least 95% identical to the sequence of SEQ ID NO.: 17.

2. The method of claim 1 , wherein the subject in need of G-CSF administration has or is suspected of having a disease, and the synthetic mRNA encoding a G-CSF polypeptide is in an amount sufficient to modulate one or more activities associated with G-CSF to treat the disease.

3. The method of claim 1 , wherein the composition further comprises a lipid-based transfection reagent.

4. The method of claim 1 , wherein the composition further comprises a cell penetration agent.

5. The method of claim 1 , wherein the synthetic mRNA is administered to the subject in a dosage range of about 1.0 μg/kg to about 100 mg/kg of body weight.

6. The method of claim 1 , wherein the subject is human.

7. The method of claim 1 , wherein the administration is repeated two, three, four, five or more than five times.

8. The method of claim 1 , wherein the administration occurs once daily.

9. The method of claim 1 , wherein the administration occurs once every two days.

10. The method of claim 1 , wherein the composition is administered to the subject via an intravenous injection.

11. The method of claim 1 , wherein the composition is administered to the subject via a subcutaneous injection.

12. The method of claim 1 , further comprising administering an effective amount of AMD3100 (1,1′-[1,4-phenylene-bis(methylene)]-bis-1,4,8,11-tetraazacyclotetradecane) to the subject after administering the composition.

13. The method of claim 12 , wherein the composition is administered at least twice but fewer than ten times prior to administering the AMD3100.

14. The method of claim 1 , wherein the composition further comprises a synthetic messenger ribonucleic acid (mRNA) encoding i) a macrophage inflammatory protein (MIP) polypeptide or ii) an antibody that prevents EGF binding to EGFR.

15. A method of efficient protein production in a cell population, the method comprising contacting a cell population with a modified nucleic acid comprising: (i) a translatable region encoding a recombinant polypeptide; and (ii) at least one nucleoside modification, under conditions such that an effective amount of the protein is present in the cell population, wherein the recombinant polypeptide is a granulocyte colony-stimulating factor (G-CSF) polypeptide and wherein the nucleic acid is a synthetic mRNA, and the synthetic mRNA sequence is at least 95% identical to the sequence of SEQ ID NO.: 17.

16. A method for inducing in vivo translation of a recombinant polypeptide in a mammalian subject in need thereof, comprising administering to the subject an effective amount of a composition comprising a nucleic acid comprising: (i) a translatable region encoding a recombinant polypeptide; and (ii) at least one nucleoside modification, under conditions such that the nucleic acid is localized into a cell of the subject and the recombinant polypeptide is capable of being translated in the cell from the nucleic acid, wherein the recombinant polypeptide is a granulocyte colony-stimulating factor (G-CSF) polypeptide and wherein the nucleic acid is a synthetic mRNA, and the synthetic mRNA sequence is at least 95% identical to the sequence of SEQ ID NO.: 17.

17. The method of claim 1 , wherein the mRNA comprises pseudouridine, 5′-methylcytidine, or a combination thereof.

18. The method of claim 15 , wherein the mRNA comprises pseudouridine, 5′-methylcytidine, or a combination thereof.

19. The method of claim 16 , wherein the mRNA comprises pseudouridine, 5′-methylcytidine, or a combination thereof.

20. The method of claim 1 , wherein 100% of cytidine and uridine nucleosides of the synthetic messenger ribonucleic acid are modified.

21. The method of claim 15 , wherein 100% of cytidine and uridine nucleosides of the synthetic messenger ribonucleic acid are modified.

22. The method of claim 16 , wherein 100% of cytidine and uridine nucleosides of the synthetic messenger ribonucleic acid are modified.

23. The method of claim 1 , wherein the synthetic messenger ribonucleic acid (mRNA) is identical to the sequence of SEQ ID NO.: 18.

24. The method of claim 15 , wherein the synthetic messenger ribonucleic acid (mRNA) is identical to the sequence of SEQ ID NO.: 18.

25. The method of claim 16 , wherein the synthetic messenger ribonucleic acid (mRNA) is identical to the sequence of SEQ ID NO.: 18.

26. The method of claim 1 , wherein the synthetic messenger ribonucleic acid (mRNA) is encapsulated in a nanoparticle.

27. The method of claim 1 , wherein the synthetic messenger ribonucleic acid (mRNA) is complexed in liposomal form.

28. The method of claim 1 , wherein the administration of the synthetic messenger ribonucleic acid (mRNA) encoding a granulocyte colony-stimulating factor (G-CSF) elevates total white blood cell count in the subject.

29. A method of accelerating recovery from neutropenia, the method comprising administering to a subject in need of such recovery a composition comprising a synthetic messenger ribonucleic acid (mRNA) encoding a granulocyte colony-stimulating factor (G-CSF) polypeptide in an amount sufficient to accelerate recovery from neutropenia, wherein the synthetic mRNA sequence is at least 95% identical to the sequence of SEQ ID NO.: 17.

30. The method of claim 29 , wherein the subject is human.

31. The method of claim 30 , wherein the subject in need of recovery is a cancer patient.

32. The method of claim 31 , wherein the cancer patient has undergone chemotherapy or irradiation.

33. The method of claim 32 , wherein the cancer patient that has undergone chemotherapy or irradiation is a patient receiving a stem cell transplant.

34. The method of claim 29 , wherein the composition further comprises a pharmaceutically acceptable carrier.