Methods and compositions for delivering mRNA coded antibodies
View Patent ↗The present invention provides, among other things, methods and compositions for delivering an antibody in vivo by administering to a subject in need thereof one or more mRNAs encoding a heavy chain and a light chain of an antibody, and wherein the antibody is expressed systemically in the subject. In some embodiments, the one or more mRNAs comprise a first mRNA encoding the heavy chain and a second mRNA encoding the light chain of the antibody.
1. A method of delivering an antibody in vivo, the method comprising:
administering systemically to a subject in need thereof a first mRNA polynucleotide encoding a heavy chain and a second mRNA polynucleotide encoding a light chain of the antibody,
wherein the first mRNA polynucleotide and the second mRNA polynucleotide are separate, each comprising SEQ ID NO: 9 encoding a signal peptide sequence;
wherein the first mRNA and the second mRNA are encapsulated in liposomes, each liposome comprising a cationic lipid, a non-cationic lipid and a PEG-modified lipid; and
wherein the antibody is detectable in the serum of the subject for more than 72 hours post-administration.
2. The method of claim 1 , wherein the first mRNA polynucleotide and the second mRNA polynucleotide are present at a ratio ranging between approximately 10:1 to 1:10.
3. The method of claim 2 , wherein the first mRNA polynucleotide and the second mRNA polynucleotide are present at a ratio of approximately 4:1.
4. The method of claim 2 , wherein the first mRNA polynucleotide-and the second mRNA polynucleotide are present at a ratio of approximately 1:1.
5. The method of claim 1 , wherein the each liposome comprises cationic lipids, neutral lipids, cholesterol-based lipids, and PEG-modified lipids.
6. The method of claim 1 , wherein the liposomes have an average size no greater than about 150 nm, 100 nm, or 75 nm.
7. The method of claim 1 , wherein the first and second mRNA polynucleotides are modified to include a modified nucleotide.
8. The method of claim 1 , wherein the first and second mRNA polynucleotides are unmodified.
9. The method of claim 1 , wherein the first and second mRNAs are administered intravenously or intraperitoneally.
10. The method of claim 1 , wherein the antibody is detectable in the serum of the subject at least about, 96 hours or 120 hours post-administration.
11. The method of claim 1 , wherein the antibody is an intact immunoglobulin.
12. The method of claim 1 , wherein the first mRNA and the second mRNA polynucleotides are encapsulated in a same liposome.
13. The method of claim 1 , wherein the first mRNA and the second mRNA polynucleotides are encapsulated in separate liposomes.
14. The method of claim 1 , wherein the cationic lipids constitute 5% to 50% of the total lipids in the liposome.
15. The method of claim 1 , wherein the cationic lipids constitute 10% to 40% of the total lipids in the liposome.
16. The method of claim 1 , wherein the PEG-modified lipids constitute 0.5% to 20% of the total lipids in the liposome.
17. The method of claim 1 , wherein the PEG-modified lipids constitute 4% to 10% of the total lipids in the liposome.