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. A composition comprising:
a first isolated messenger ribonucleic acid (mRNA) encoding a first polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 11 and SEQ ID NO: 17, wherein said first polypeptide is a membrane-stabilized human LIGHT polypeptide;
a second isolated mRNA encoding interleukin-12 (IL-12), wherein the IL-12 comprises the amino acid sequence of SEQ ID NO:21;
and a third isolated mRNA encoding HPV16 E6 E7, wherein the HPV16 E6 E7 comprises an amino acid sequence selected from the group consisting of SEQ ID NO:24 and SEQ ID NO:27.
2. The composition of claim 1 , wherein the first isolated mRNA has at least about 80% nucleic acid sequence identity to SEQ ID NO: 12 or SEQ ID NO: 18.
3. The composition of claim 1 , wherein the second isolated mRNA has at least about 80% nucleic acid sequence identity to SEQ ID NO:20.
4. The composition of claim 1 , wherein the third isolated mRNA has at least about 80% nucleic acid sequence identity to SEQ ID NO:23 or SEQ ID NO:26.
5. The composition of claim 1 , wherein the first isolated mRNA, second isolated mRNA, and/or third isolated mRNA is at least partially encapsulated with a delivery vehicle.
6. The composition of claim 5 , wherein the delivery vehicle has a particle size less than or equal to about 200 nm.
7. The composition of claim 5 , 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.
8. 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.
9. The composition of claim 8 , wherein the compound is selected from the group consisting of:
and pharmaceutically acceptable salts of the compound.
10. The composition of claim 1 , wherein the composition is a therapeutic composition or a vaccine.
11. The composition of claim 10 , wherein the composition is a human papillomavirus (HPV) mRNA vaccine.
12. The composition of claim 10 , 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.
13. The composition of claim 10 , wherein the composition is configured to be administered as an injectable preparation.
14. The composition of claim 10 , wherein the composition is configured to be administered to a subject known to have cervical dysplasia or cervical intraepithelial neoplasia.
15. The composition of claim 14 , wherein the composition is configured as an injectable preparation for administration into a cervix of the subject.
16. The composition of claim 10 , wherein the composition further comprises one or more one or more therapeutically acceptable carriers, therapeutically acceptable diluents, therapeutically acceptable excipients or other therapeutic agents.
17. The composition of claim 16 , 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.