mRNA FOR USE IN TREATMENT OF HUMAN GENETIC DISEASES
Compositions for modulating the expression of a protein in a target cell comprising at least one RNA molecule which comprises at least one modification 5 conferring stability to the RNA, as well as related methods, are disclosed.
1 . A composition for modulating the expression of a protein in a target cell, wherein said composition comprises at least one RNA molecule and a transfer vehicle and wherein the RNA comprises at least one modification which confers stability to the RNA.
2 . The composition of claim 1 , wherein the RNA molecule is selected from the group consisting of mRNA, miRNA, snRNA, and snoRNA.
3 . The composition of claim 1 , wherein the RNA molecule comprises more than one modification which confers stability to the RNA molecule.
4 . The composition of claim 1 , wherein the RNA molecule comprises a modification of the 5′ untranslated region of said RNA molecule.
5 . The composition of claim 4 , wherein said modification comprises a partial sequence of a CMV immediate-early 1 (IE 1) gene.
6 . The composition of claim 5 , wherein said partial sequence of the CMV immediate-early 1 (IEI) gene comprises SEQ ID NO: 2 or SEQ ID NO: 1.
7 . The composition of claim 4 , wherein said modification comprises the inclusion of a poly A tail.
8 . The composition of claim 4 , wherein said modification comprises the inclusion of a Cap 1 structure.
9 . The composition of claim 1 , wherein the RNA molecule comprises a modification of the 3′ untranslated of said RNA molecule.
10 . The composition of claim 9 , wherein said modification comprises the inclusion of a sequence encoding human growth hormone (hGH).
11 . The composition of claim 10 , wherein said sequence encoding human growth hormone (hGH) comprises SEQ ID NO: 3.
12 . The composition of claim 9 , wherein said modification comprises the inclusion of a poly A tail.
13 . The composition of claim 1 , wherein the RNA encodes ornithine carbamoyl transferase.
14 . The composition of claim 1 , wherein the RNA encodes alpha galactosidase.
15 . The composition of claim 1 , wherein the RNA encodes erythropoietin.
16 . A method of treating a subject deficient in a protein, comprising administering a composition comprising an mRNA and a transfer vehicle, wherein the mRNA encodes a functional protein corresponding to the protein which is deficient in the subject, and wherein the mRNA comprises at least one modification which confers stability to the administered mRNA.
17 . The method claim 16 , wherein following expression of said mRNA by a target cell a functional protein is produced.
18 . The method of claim 17 , wherein said functional protein is secreted from said target cell.
19 . The method of claim 16 , wherein said mRNA encodes ornithine carbamoyltransferase.
20 . The method of claim 16 , wherein said mRNA encodes alpha galactosidase.