In vivo production of proteins
AssigneeModernaTX, Inc.
InventorsAntonin DE FOUGEROLLES, Justin Guild
Life of this patent
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Abstract
The invention relates to compositions including polynucleotides encoding polypeptides which have been chemically modified by replacing the uridines with 1-methyl-pseudouridine to improve one or more of the stability and/or clearance in tissues, receptor uptake and/or kinetics, cellular access by the compositions, engagement with translational machinery, mRNA half-life, translation efficiency, immune evasion, protein production capacity, secretion efficiency, accessibility to circulation, protein half-life and/or modulation of a cell's status, function, and/or activity.
Claims12
A method of producing a polypeptide of interest in vivo comprising contacting a mammalian cell, tissue or organism with at least one isolated mRNA encoding the polypeptide of interest;
- wherein the polypeptide of interest is selected from the group consisting of aldolase A, fructose-bisphosphate (ALDOA), alpha- methylacyl-CoA racemase (AMACR), amyloid P component, serum (APCS), angiopoietin 1 (ANGPT1), apolipoprotein A-1 (APOA1) Milano, apolipoprotein A-1 (APOA1) Paris, apolipoprotein A-1 (APOA1), argininosuccinate lyase (ASL), artemin (ARTN), arylsulfatase B (ARSB), bactericidal/permeability-increasing protein (rBPI-21), bone morphogenetic protein 2 (BMP2), bone morphogenetic protein 7 (BMP7), branched chain keto acid dehydrogenase El, alpha polypeptide (BCKDHA), colony stimulating factor 2 (granulocyte- macrophage) (GM-CSF), colony stimulating factor 3 (granulocyte) (GCSF), deoxyribonuclease I (DNAsel), erythropoietin (EPO), factor IX, factor VII, factor XI, fibrinogen A (FGA), fibroblast growth factor 18 (FGF18), fibroblast growth factor 23 (FGF23), fibroblast growth factor 7 (FGF7 or KGF), follistatin (FST), fumarylacetoacetate hydrolase (fumarylacetoacetase) (FAH), galactokinase 1 (GALK1), galactosidase, alpha (GLA), glucan (1,4-alpha-), branching enzyme 1 (GBE1), glycoprotein hormones, alpha polypeptide (CGA or FSH-alpha), hemoglobin, beta (HBB), hepatocyte growth factor (HGF), human growth hormone (hGH), insulin aspart, insulin glargine, insulin glulisine, insulin lispro, Interferon beta (IFNB), interferon, alpha 2 (IFNA2), interleukin 10 (IL- 10), interleukin 15 (IL-15), Interleukin 7 (IL-7), klotho (KL), lecithin-cholesterol acyltransferase (LCAT), lipase A, lysosomal acid, cholesterol esterase (LIPA), lipoprotein lipase (LPL), low density lipoprotein receptor (LDLR), mannosidase, alpha, class 2B, member 1 (MAN2B1), microsomal triglyceride transfer protein (MTTP), N-acetylglutamate synthase (NAGS), neuregulin 1 (NRG1), ornithine carbamoyltransferase (OTC), phosphorylase kinase, alpha 2 (liver) (PHKA2), plasminogen (PLAT), septin 4 (ARTS or SEPT4), serpin peptidase inhibitor, clade C (antithrombin), member 1 (SERPINC1), serpin peptidase inhibitor, clade F (alpha-2 antiplasmin, pigment epithelium derived factor), member 2 (SERPINF2), sirtuin 1 (SIRT1), sirtuin 6 (SIRT6), solute carrier family 16, member 3 (monocarboxylic acid transporter 4) (SLC16A3), solute carrier family 2 (facilitated glucose transporter), member 1 (SLC2A1 or GLUT1), sortilin 1 (SORT1), Thrombopoietin (THPO), transforming growth factor, beta (TGFB1), tuftelin 1 (TUFT1), tumor protein p53 (TP53), tyrosinase (TYR), UDP glucuronosyltransferase 1 family, polypeptide A 1 (UGT1A1), vascular endothelial growth factor (VEGF) and X-linked inhibitor of apoptosis (XI AP).
Dependencies are inferred from the claim text.