Uses of modified rna encoding retinaldehyde dehydrogenase
AssigneePresident and Fellows of Harvard College
InventorsUlrich H. von Andrian, Bruno Raposo
Life of this patent
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Abstract
Some aspects of this disclosure provide modified mRNA (modRNA) encoding retinaldehyde dehydrogenase (RALDH) enzyme, in addition to methods of synthesis, administration, use, and treatment. In some embodiments, the modRNA may be used in a vaccine to treat infections (e.g., mucosal infections) and/or cancers (e.g., mucosal cancers).
Claims21
1-160. (canceled)
A method of inducing an antigen-specific immune response in the gastrointestinal tract of a subject, the method comprising administering a therapeutically effective amount of a mucosal vaccine to the subject to produce the antigen-specific immune response,
- wherein the mucosal vaccine comprises:
- (a) an antigen from a mucosal pathogen;
- and
- (b) a messenger ribonucleic acid (mRNA) polynucleotide comprising an open reading frame (ORF) encoding a retinaldehyde dehydrogenase (RALDH) protein, wherein the mRNA polynucleotide has been modified such that at least 50% of the uridine residues are pseudouridine, and at least 50% of the cytidine residues are 5-methylcytidine.
A method of inducing an antigen-specific immune response in the gastrointestinal tract of a human subject, the method comprising administering a therapeutically effective amount of a mucosal vaccine to the human subject to produce the antigen-specific immune response,
- wherein the mucosal vaccine comprises:
- (a) an antigen from a mucosal pathogen;
- (b) a messenger ribonucleic acid (mRNA) polynucleotide comprising an open reading frame (ORF) encoding a human retinaldehyde dehydrogenase 2 (RALDH2) protein, wherein the human RALDH2 protein comprises an amino acid sequence having at least 90% identity to SEQ ID NO:
- 5, wherein the mRNA polynucleotide has been modified such that 100% of the uridine residues are pseudouridine, and 100% of the cytidine residues are 5-methylcytidine, and wherein the mRNA is encapsulated in a lipid nanoparticle;
- and
- (c) retinol.
Dependencies are inferred from the claim text.