Stabilized polyribonucleotide coding for an elastic fibrous protein

Abstract

The invention relates to a polyribonucleotide, a cosmetic and pharmaceutical compound that has the polyribonucleotide and a medicinal product that has the polyribonucleotide and the compound.

What is claimed is: 
     
         1 . Polyribonucleotide encoding an elastic fibrous protein having a nucleotide sequence comprising at least one said polyribonucleotide stabilizing chemical modification. 
     
     
         2 . Polyribonucleotide of  claim 1 , wherein the elastic fibrous protein is selected from the group consisting of: elastin/tropoelastin, fibrillin, micro-fibrills associated glycoprotein (MAGP), fibuline, elastin-micro-fibrills-interface localized protein (EMILIN), lysyl oxidase (LOX), and precursors thereof. 
     
     
         3 . Polyribonucleotide of  claim 1  which is an mRNA. 
     
     
         4 . Polyribonucleotide of  claim 1 , wherein the at least one polyribonucleotide stabilizing chemical modification comprises a chemically modified uridine or cytidine. 
     
     
         5 . Polyribonucleotide of  claim 4 , wherein the chemically modified uridine is selected from the group consisting of: pseudouridine, 2-thiouridine, 5-methyluridine, 5-methyluridine-5′-triphosphate (m5U), 5-idouridine-5′-triphosphate (15U), 4-thiouridine-5′-triphosphate (S4U), 5-bromouridine-5′-triphosphate (Br5U), 2′-methyl-2′-deoxyuridine-5′-triphosphate (U2′m), 2′-amino-2′-deoxyuridine-5′-triphosphate (U2′NH2), 2′-azido-2′-deoxyuridine-5′-triphosphate (U2′N3), 2′-fluoro-2′-deoxyuridine-5′-triphosphate (U2′F) and combinations thereof. 
     
     
         6 . Polyribonucleotide of  claim 4 , wherein the chemically modified cytidine is selected from the group consisting of: 5-methylcytidine, 3-methylcytidine, 2-thiocytidine, 2′-methyl-2′-deoxcytidin-5′-triphosphate (C2′m), 2′-amino-2′-deoxycytidine-5′-triphosphate (C2′NH2), 2′-fluoro-2′-deoxycytidine-5′-triphosphate (C2′F), 5-iodcytidine-5′-triphosphate (I5U), 5-bromocytidine-5′-triphosphate (Br5U), 2′-azido-2′-deoxycytidine-5′-triphosphate (C2′N3) and combinations thereof. 
     
     
         7 . Polyribonucleotide of  claim 1 , wherein the chemical modification is selected from the group consisting of: 5 cap structure, preferably a 5′ guanine cap, poly (A) tail, a cap structure analog [anti-reverse cap analog (ARCA; 3′O-Me-m 7 G(5′)ppp(5′)ppp(5′)G)], a strengthening of the translation-initiation sequence at the start codon AUG by the sequence (CCCCGC)aucGagAUG. 
     
     
         8 . Polyribonucleotide of  claim 1 , comprising a ribonucleotide sequence where at least approx. 25% of the uridines, or where at least approx. 25% of the cytidines are chemically modified. 
     
     
         9 . Polyribonucleotide of  claim 1 , comprising the sequence of SEQ ID No. 1, where at least approx. 25% of the uridines, or where at least approx. 25% of the cytidines are chemically modified. 
     
     
         10 . Polyribonucleotide of  claim 1 , encoding an amino acid sequence selected from the group consisting of: SEQ ID No. 7, SEQ ID No. 8, SEQ ID No. 9, SEQ ID No. 10, and SEQ ID No. 11. 
     
     
         11 . Polyribonucleotide of  claim 1 , configured for any of the following indications: the induction of the synthesis of an elastic fibrous protein, in age-related loss of elasticity of the skin (wrinkle formation), for promoting the wound healing, for the recovery of the elasticity of vaginal tissue, soft and hard tissue of the periodontium. 
     
     
         12 . Polyribonucleotide of  claim 1  configured for the treatment of a deficient synthesis of elastic fibrous protein. 
     
     
         13 . Polyribonucleotide of  claim 1  configured for the treatment of a disease selected from the group consisting of: arteriosclerosis, aortic stenosis, aortic aneurysm, pulmonary emphysema, dermatochalasis, Williams-Beuren syndrome, sub valvular innate aortic stenosis (SVAS). 
     
     
         14 . Cosmetic composition, comprising the polyribonucleotide of  claim 1  and a cosmetically acceptable formulation. 
     
     
         15 . Pharmaceutical composition, comprising the polyribonucleotide of  claim 1  and a pharmaceutically acceptable formulation. 
     
     
         16 . Medical product comprising the polyribonucleotide of  claim 1  or the composition of  claim 15 . 
     
     
         17 . Medical product of  claim 16  which is coated with the polyribonucleotide of  claim 1  or the composition of  claim 15 . 
     
     
         18 . Medical product of  claim 16  which is selected from the group consisting of: medical patch, vascular implant, and stent.