MRNA therapeutic compositions
The present disclosed and described technology are directed to multimodal mRNA-based immunotherapies that deliver both antigens and immunomodulators. Related formulations, method of administration, and kits are disclosed and described.
1. An isolated messenger ribonucleic acid (mRNA) encoding a polypeptide comprising an amino acid sequence selected from the group consisting SEQ ID NO: 11 and SEQ ID NO: 17, wherein said polypeptide is a membrane-stabilized human LIGHT polypeptide.
2. The isolated mRNA of claim 1 , wherein the isolated mRNA has at least about 80% nucleic acid sequence identity to SEQ ID NO: 12 or SEQ ID NO: 18.
3. A composition comprising the isolated mRNA of claim 1 , wherein the isolated mRNA is at least partially encapsulated with a delivery vehicle.
4. The composition of claim 3 , wherein the delivery vehicle has a particle size less than or equal to about 200 nm.
5. The composition of claim 3 , wherein the delivery vehicle is selected from the group consisting of amphipathic molecules, amino-lipidated peptides, tertiary amino lipidated cationic peptides, a cationic component, a peptoid, a lipoid, a liposome, a lipoplex, a lipid nanoparticle, a cationic lipid nanoparticle, a polymeric compound, and a conjugate.
6. The composition of claim 5 , wherein the delivery vehicle comprises at a compound or pharmaceutically acceptable salt of the compound having a having formula (I)
wherein n is 1, 2, 3, 4, 5, or 6; R 1 is H, C 1-3 alkyl, or hydroxyethyl; and each R 2 independently is C 8-24 alkyl or C 8-24 alkenyl.
7. The composition of claim 6 , wherein the compound is selected from the group consisting of:
and pharmaceutically acceptable salts of the compound.
8. The composition of claim 3 , wherein the composition further comprises a second isolated mRNA that encodes a pro-inflammatory cytokine, wherein the pro-inflammatory cytokine is interleukin-12.
9. The composition of claim 8 , wherein the pro-inflammatory cytokine comprises the amino acid sequence identified as SEQ ID NO:21.
10. The composition of claim 8 , wherein the second isolated mRNA has at least about 80% nucleic acid sequence identity to SEQ ID NO:20.
11. The composition of claim 3 , wherein the composition further comprises an additional isolated mRNA that encodes an antigen, wherein the antigen is HPV16 E6 E7.
12. The composition of claim 11 , wherein the antigen has an amino acid sequence identified as SEQ ID NO:24 or SEQ ID NO:27.
13. The composition of claim 11 , wherein the additional isolated mRNA has at least about 80% nucleic acid sequence identity to SEQ ID NO:23 or SEQ ID NO:26.
14. The composition of claim 3 , wherein the composition is a therapeutic composition or a vaccine.
15. The composition of claim 14 , wherein the composition is a human papillomavirus (HPV) mRNA vaccine.
16. The composition of claim 14 , wherein the composition is configured to be administered to a subject known to have cervical cancer, HPV-driven cancer, or a disease associated with HPV.
17. The composition of claim 14 , wherein the composition is configured to be administered as an injectable preparation.
18. The composition of claim 14 , wherein the composition further comprises one or more one or more therapeutically acceptable carriers, therapeutically acceptable diluents, therapeutically acceptable excipients or other therapeutic agents.
19. The composition of claim 18 , wherein the therapeutically acceptable excipients are selected from the group consisting of salts, buffering agents, preservatives, antiadherents, antioxidants, binders, coatings, compression aids, disintegrants, dyes, emollients, emulsifiers, fillers, film formers, coatings, flavors, fragrances, glidants, lubricants, sorbents, suspending or dispersing agents, sweeteners, and waters of hydration.