Aminoacyl tRNA synthetases for modulating inflammation
Inflammatory and other cellular response-modulating compositions are provided comprising aminoacyl-tRNA synthetase polypeptides, including active fragments and/or variants thereof. Also provided are methods of using such compositions in the treatment of conditions that benefit from the modulation of inflammation, such as inflammatory diseases or conditions.
1. A composition comprising: a modified mRNA polynucleotide encoding a histidyl tRNA synthetase (HRS) polypeptide and a physiologically-acceptable carrier, where the HRS polypeptide is selected from (a) SEQ ID NO:28, (b) a fragment of SEQ ID NO:28 comprising at least 400 contiguous amino acids of SEQ ID NO:28, and (c) a variant which differs from SEQ ID NO: 28 by less than 10% of the residues of SEQ ID NO: 28, where the modified mRNA polynucleotide is operably linked to a heterologous translational regulatory element.
2. The composition of claim 1 , which is an aqueous solution suitable for intravenous administration to a mammalian subject in need thereof.
3. The composition of claim 1 , comprising liposomes, nanocapsules, microparticles, microspheres, lipid particles, or vesicles.
4. The composition of claim 1 , which is formulated for delivery encapsulated in a lipid particle, a liposome, a vesicle, nanosphere, or a nanoparticle.
5. The composition of claim 1 , where the heterologous translational regulatory element comprises an initiation signal.
6. The composition of claim 1 , where (b) is a fragment of SEQ ID NO:28 comprising at least 500 contiguous amino acids of SEQ ID NO:28.
7. The composition of claim 1 , where (c) is a variant which differs from SEQ ID NO:28 by less than 5% of the residues of SEQ ID NO:28.