Modified polynucleotides for the production of factor ix

Abstract

Provided are formulations, compositions and methods for delivering biological moieties such as modified nucleic acids into cells to modulate protein expression. Such compositions and methods include the delivery of biological moieties, and are useful for production of proteins.

We claim: 
     
         1 . An isolated polynucleotide comprising a sequence having at least 70% identity to SEQ ID NO: 8. 
     
     
         2 . The isolated polynucleotide of  claim 1  comprising SEQ ID NO: 8. 
     
     
         3 . The isolated polynucleotide of  claim 2 , wherein the isolated polynucleotide is an mRNA. 
     
     
         4 . The isolated polynucleotide of  claim 3  comprising at least one nucleoside modification. 
     
     
         5 . The isolated polynucleotide of  claim 3 , wherein the mRNA has a 5′ cap and wherein the 5′Cap is Cap1. 
     
     
         6 . The isolated polynucleotide of  claim 5 , wherein the mRNA has a polyA tail and wherein the polyA tail is approximately 160 nucleotides in length. 
     
     
         7 . A pharmaceutical composition comprising the isolated polynucleotide of  claim 3 . 
     
     
         8 . The pharmaceutical composition of  claim 7  which is formulated and wherein the formulation is a lipid formulation. 
     
     
         9 . A method of producing a polypeptide of interest in a cell, tissue or bodily fluid of a mammalian subject in need thereof comprising administering to said subject a pharmaceutical composition comprising the isolated polynucleotide of  claim 3 . 
     
     
         10 . The method of  claim 9 , wherein the isolated polynucleotide further comprises a 5′Cap1 structure and a polyA tail of approximately 160 nucleotides in length. 
     
     
         11 . The method of  claim 10 , wherein the pharmaceutical composition is formulated. 
     
     
         12 . The method of  claim 11 , wherein the formulation is a lipid formulation. 
     
     
         13 . The method of  claim 9 , where the pharmaceutical composition is administered at a total dose of about 0.1 mg/kg to about 40 mg/kg. 
     
     
         14 . The method of  claim 13 , wherein administration occurs on a schedule selected from the group consisting of three time a day, twice a day, once a day, every other day, every third day, weekly, biweekly, every three weeks, every four weekly, and monthly. 
     
     
         15 . The method of  claim 13 , wherein the total dose is administered by multiple administrations. 
     
     
         16 . The method of  claim 15 , wherein the multiple administrations occur on a schedule selected from the group consisting of three times a day, twice a day, once a day, every other day, every third day, weekly, biweekly, every three weeks, every four weekly, and monthly. 
     
     
         17 . The method of  claim 9 , wherein an increase in the level of the polypeptide of interest is observed in tissue or bodily fluid within 8 hours. 
     
     
         18 . The method of  claim 9 , wherein an increase in the level of the polypeptide of interest is observed in tissue or bodily fluid within 2 hours. 
     
     
         19 . The method of  claim 18 , wherein the increased level of the polypeptide of interest is observed in a tissue selected from the group consisting of liver, spleen, kidney, lung, heart, peri-renal adipose tissue, thymus and muscle.