Treatment of hyperbilirubinemia

Abstract

The invention relates to a nucleic acid sequence useful in the treatment of hyperbilirubinemia, in particular in the treatment of Crigler-Najjar syndrome. More particularly, the nucleic acid sequence of the present invention is a codon-optimized UGT1A1 coding sequence.

We claim: 
     
         1 . An intron which is a modified intron with decreased open reading frames. 
     
     
         2 . The intron according to  claim 1 , which is a modified HBB2 intron, a modified FIX intron, or a modified chicken beta-globin intron. 
     
     
         3 . A nucleic acid construct comprising the intron according to  claim 1 . 
     
     
         4 . The nucleic acid construct according to  claim 3 , further comprising a gene of interest and one or more additional expression control sequences. 
     
     
         5 . The nucleic acid construct according to  claim 4 , wherein the said additional expression control sequence is an ubiquitous or tissue-specific promoter. 
     
     
         6 . A vector comprising the intron according to  claim 1 . 
     
     
         7 . The vector according to  claim 6 , which is a viral vector. 
     
     
         8 . The vector according to  claim 7 , wherein said viral vector is a single-stranded or double-stranded self-complementary AAV vector. 
     
     
         9 . The vector according to  claim 8 , wherein the AAV vector has an AAV-derived capsid. 
     
     
         10 . The vector according to  claim 9 , wherein the AAV vector has an AAV8 capsid. 
     
     
         11 . The vector according to  claim 9 , wherein the AAV vector is a pseudotyped AAV vector. 
     
     
         12 . A cell transformed with the nucleic acid construct according to  claim 3 . 
     
     
         13 . A method of gene or cell therapy in a subject comprising expressing a nucleic acid construct according to  claim 4  in a subject in need of gene or cell therapy.