Engineered nucleic acids and methods of use thereof
View Patent ↗Provided are compositions and methods for delivering biological moieties such as modified nucleic acids into cells to modulate protein expression. Such compositions and methods include the use of modified messenger RNAs, and are useful to treat or prevent diseases, disorders or conditions, or to improve a subject's heath or wellbeing.
1. A pharmaceutical formulation comprising:
i) an effective amount of a messenger ribonucleic acid (mRNA) sequence encoding a melanocyte-stimulating hormone polypeptide, wherein the mRNA sequence is at least 90% identical to the sequence of SEQ ID NO: 19, and wherein the mRNA sequence comprises an open reading frame encoding SEQ ID NO: 10; and
ii) a pharmaceutically acceptable carrier,
wherein the formulation is suitable for repeated administration to a mammalian subject in need thereof.
2. The pharmaceutical formulation of claim 1 , further comprising a lipid-based transfection reagent.
3. The pharmaceutical formulation of claim 1 , wherein administration occurs at least once a day for 3 days.
4. The pharmaceutical formulation of claim 3 , wherein administration occurs three times a day for 3 days.
5. The pharmaceutical formulation of claim 1 , wherein the effective amount of mRNA is selected from the group consisting of 100 ng, 250 ng, 500 ng, 1000 ng and 1500 ng.
6. A pharmaceutical formulation comprising:
i) an effective amount of an mRNA sequence encoding a melanocyte-stimulating hormone polypeptide, wherein the mRNA sequence is at least 90% identical to the sequence of SEQ ID NO: 19, and wherein the mRNA sequence comprises an open reading frame encoding SEQ ID NO: 10;
ii) a cell penetration agent; and
iii) a pharmaceutically acceptable carrier,
wherein the formulation is suitable for repeated administration to a mammalian subject in need thereof.
7. The pharmaceutical formulation of claim 6 , further comprising a lipid-based transfection reagent.
8. The pharmaceutical formulation of claim 6 , wherein administration occurs at least once a day for 3 days.
9. The pharmaceutical formulation of claim 8 , wherein administration occurs three times a day for 3 days.
10. The pharmaceutical formulation of claim 6 , wherein the effective amount of mRNA is selected from the group consisting of 100 ng, 250 ng, 500 ng, 1000 ng and 1500 ng.
11. An mRNA sequence encoding a melanocyte-stimulating hormone polypeptide, wherein the mRNA sequence is at least 90% identical to the sequence of SEQ ID NO: 19, and wherein the mRNA sequence comprises an open reading frame encoding SEQ ID NO: 10.
12. The mRNA sequence of claim 11 , wherein the mRNA sequence comprises pseudouridine and 5-methyl-cytidine.
13. The mRNA sequence of claim 12 , wherein the mRNA sequence comprising pseudouridine and 5-methyl-cytidine is SEQ ID NO: 20.