Novel Therapeutical Tools and Methods for Treating Blindness

Abstract

The present inventions relates to the use of an isolated nucleic acid molecule comprising a nucleotide sequence coding for a hyperpolarizing light-gated ion channel or pump gene from an archeon or for a light-active fragment of said gene, or the nucleotide sequence complementary to said nucleotide sequence, for treating or ameliorating blindness. The light-gated ion channel or pump gene can be a halorhodopsin gene.

1 . An isolated nucleic acid molecule comprising a nucleotide sequence coding for a hyperpolarizing light-gated ion channel or pump gene from an archeon or for a light-active fragment of said gene, or the nucleotide sequence complementary to said nucleotide sequence, for use in treating or ameliorating blindness. 
     
     
         2 . The isolated nucleic acid molecule of  claim 1  wherein the light-gated ion channel or pump gene is a halorhodopsin gene. 
     
     
         3 . The isolated nucleic acid molecule of  claim 1  wherein the hyperpolarizing light-gated ion channel or pump gene is the halorhodopsin gene from  Natronomas pharaonis  (NpHR). 
     
     
         4 . The isolated nucleic acid molecule of  claim 1  wherein said isolated nucleic acid molecule is for use by administration and expression in at least one of cones, rods, horizontal cells, rod bipolar cells, ON-cone bipolar cells, OFF-cone bipolar cells, amacrine cells, ganglion cells. 
     
     
         5 . The isolated nucleic acid molecule of  claim 1  comprising a cell specific promoter, for instance human rhodopsin promoter, human red opsin promoter the Grm6 promoter controlling the expression of the light-gated ion channel or pump gene. 
     
     
         6 . The isolated nucleic acid molecule of  claim 1  wherein said hyperpolarizing light-gated ion channel or pump gene is used, simultaneously or sequentially, together with a depolarizing light-gated ion channel gene. 
     
     
         7 . The isolated nucleic acid molecule of  claim 6  wherein the depolarizing light-gated ion channel gene is a channelrhodopsin, for instance channelrhodopsin-2. 
     
     
         8 . The isolated nucleic acid molecule of  claim 6  wherein the expression of said depolarizing light-gated ion channel gene is under the control of human rhodopsin promoter, human red opsin promoter and the Grm6 promoter. 
     
     
         9 . An isolated nucleic acid molecule useful for treating blindness comprising a nucleic acid sequence coding for a hyperpolarizing light-gated ion channel or pump gene and a nucleic acid sequence coding for a depolarizing light-gated ion channel or pump gene. 
     
     
         10 . The isolated nucleic acid molecule of  claim 9  wherein said hyperpolarizing light-gated ion channel or pump gene is halorhodopsin, for instance the halorhodopsin gene from  Natronomas pharaonis  (NpHR), and said a depolarizing light-gated ion channel gene is a channelrhodopsin, for instance channelrhodopsin-2. 
     
     
         11 . The isolated nucleic acid molecule of  claim 9  wherein the hyperpolarizing light-gated ion channel or pump and the depolarizing light-gated ion channel are encoded in such a way that a fusion protein is formed upon expression. 
     
     
         12 . The isolated nucleic acid molecule of  claim 9  wherein the expression of the genes encoding the hyperpolarizing light-gated ion channel and the depolarizing light-gated ion channel or pump are, either commonly or independently, under the control of a promoter chosen from the group of human rhodopsin promoter, human red opsin promoter and the Grm6 promoter. 
     
     
         13 . A recombinant vector comprising the nucleic acid of  claim 1 . 
     
     
         14 . A host cell comprising the vector of  claim 13 . 
     
     
         15 . A kit comprising an isolated nucleic according to  claim 1 .