MRNA treatment nanoparticles
Provided herein are examples of mRNA treatment nanoparticles and methods of using them to treat a patient. An mRNA treatment nanoparticle may include one or more mRNAs encoding a tumor-specific antigen and an immunomodulatory agent; and a delivery vehicle molecule encapsulating the one or more mRNAs.
1. A therapeutic mRNA composition comprising:
a first mRNA scaffold comprising a first mRNA coding region encoding HPV16 E6 E7;
a second mRNA scaffold comprising a second mRNA coding region encoding interleukin-12, wherein the second mRNA coding region has at least about 80% nucleic acid sequence identity to SEQ ID NO:5; and
a third mRNA scaffold comprising a third mRNA coding region encoding tumor necrosis factor superfamily member 14 (TNFSF14) wherein the third mRNA coding region has at least about 80% nucleic acid sequence identity to SEQ ID NO:11, and
wherein the first mRNA scaffold, the second mRNA scaffold and, the third mRNA scaffold are encapsulated in a delivery vehicle, wherein the delivery vehicle is selected from the group consisting of lipid nanoparticles, polymer-based nanoparticles, cationic lipids, ionizable lipids, amino-lipidated peptoids, amphipathic molecules/nanoparticles, and tertiary amino lipidated cationic peptoids.
2. The therapeutic mRNA composition of claim 1 , wherein the first mRNA scaffold and the second mRNA scaffold are encapsulated in a single delivery vehicle.
3. The therapeutic mRNA composition of claim 1 , wherein the first mRNA scaffold, the second mRNA scaffold, and the third mRNA scaffold are encapsulated in a single delivery vehicle.
4. The therapeutic mRNA composition of claim 1 , wherein the interleukin-12 has at least about 80% amino acid sequence identity to SEQ ID NO:6.
5. The therapeutic mRNA composition of claim 1 , wherein the TNFSF14 has at least about 80% amino acid sequence identity to SEQ ID NO:12.
6. The therapeutic mRNA composition of claim 1 , wherein the TNFSF14 is wild type TNFSF14.
7. The therapeutic mRNA composition of claim 1 , wherein the therapeutic mRNA composition is an mRNA nanoparticle, an mRNA treatment nanoparticle, or a vaccine.
8. The therapeutic mRNA composition of claim 1 , wherein the therapeutic mRNA composition is configured to be administered to a subject known to have cervical cancer.
9. The composition of claim 1 , wherein the therapeutic mRNA composition is configured to be injected intratumorally.
10. A therapeutic mRNA composition comprising:
a single mRNA scaffold, wherein the single mRNA scaffold comprises:
a 5′ UTR,
a first immunomodulatory mRNA open reading frame encoding interleukin-12, wherein the first immunomodulatory mRNA open reading frame has at least about 80% nucleic acid sequence identity to SEQ ID NO:5,
a tumor-specific antigen mRNA open reading frame encoding HPV16 E6 E7,
a second immunomodulatory mRNA open reading frame encoding TNFSF14, wherein the second immunomodulatory mRNA open reading frame has at least about 80% nucleic acid sequence identity to SEQ ID NO:11,
and a 3′UTR,
wherein the single mRNA scaffold is encapsulated in a delivery vehicle, wherein the delivery vehicle is selected from the group consisting of wherein the delivery vehicle is selected from the group consisting of lipid nanoparticles, polymer-based nanoparticles, cationic lipids, ionizable lipids, amino-lipidated peptoids, amphipathic molecules/nanoparticles, and tertiary amino lipidated cationic peptoids.
11. The therapeutic mRNA composition of claim 10 , wherein the interleukin-12 has at least about 80% amino acid sequence identity to SEQ ID NO:6.
12. The therapeutic mRNA composition of claim 10 , wherein the TNFSF14 has at least about 80% amino acid sequence identity to SEQ ID NO:12.
13. The therapeutic mRNA composition of claim 10 , wherein the TNFSF14 is wild type TNFSF14.
14. The therapeutic mRNA composition of claim 10 , wherein the therapeutic mRNA composition is an mRNA nanoparticle, an mRNA treatment nanoparticle, or a vaccine.
15. The therapeutic mRNA composition of claim 10 , wherein the therapeutic mRNA composition is configured to be administered to a subject known to have cervical cancer.
16. The therapeutic mRNA composition of claim 10 , wherein the therapeutic mRNA composition is configured to be injected intratumorally.