Polypeptides for Specific Targeting to Otx2 Target Cells

Abstract

The invention relates to polypeptides which enable the specific targeting of a molecule of interest to homeoprotein Otx2 target cells. These polypeptides are defined by the general sequence: B 1 B 2 X 1 B 3 B 4 X 2 B 5 X 3 X 4 X 5 X 6 B 6 X 7 X 8 X 9 (SEQ ID NO: 1), in which: B 1 , B 2 , B 3 , B 4 , B 5 and B 6 are independently arginine or lysine; X 1 and X 8 are independently asparagine or glutamine; X 2 is aspartic acid or glutamic acid; X 3 , X 4 and X 6 are independently threonine or serine; X 5 is phenylalanine, tyrosine or tryptophan; X 7 represents alanine or glycine; X 9 is leucine, isoleucine or valine.

1 . A cell targeting polypeptide, characterized in that it is defined by the sequence B 1 B 2 X 1 B 3 B 4 X 2 B 5 X 3 X 4 X 5 X 6 B 6 X 7 X 8 X 9  (SEQ ID NO: 1), in which:
 B 1 , B 2 , B 3 , B 4 , B 5  and B 6  represent independently arginine or lysine;   X 1  and X 8  represent independently asparagine or glutamine;   X 2  represents aspartic acid or glutamic acid;   X 3 , X 4  and X 6  represent independently threonine or serine;   X 5  represents phenylalanine, tyrosine or tryptophan;   X 7  represents alanine or glycine;   X 9  represents leucine, isoleucine or valine' and in that, when it is placed in the presence of retinal cells, it binds specifically to ganglion neurons and to bipolar neurons.   
     
     
         2 . The cell targeting polypeptide as claimed in  claim 1 , characterized in that:
 at least one of the amino acids B 1 , B 3 , B 4 , B 5  and B 6  is an arginine; and/or   B 2  is a lysine; and/or   at least one of the amino acids X 1  and X 8  is a glutamine; and/or   X 2  is a glutamic acid; and/or   at least one of the amino acids X 3 , X 4  and X 6  is a threonine; and/or   X 5  is a phenylalanine; and/or   X 7  is an alanine; and/or   X 9  is a leucine.   
     
     
         3 . The cell targeting polypeptide as claimed in  claim 2 , characterized in that it is defined by the following sequence: RKQRRERTTFTRAQL (SEQ ID NO: 2). 
     
     
         4 . A polypeptide containing a cell targeting polypeptide as claimed  claims 1  and a transducer polypeptide. 
     
     
         5 . A composition comprising a polypeptide as claimed in  claim 1 , bonded to a second molecule. 
     
     
         6 . The composition as claimed in  claim 5 , wherein the polypetide is a chimeric polypeptide containing a polypeptide as claimed in  claim 1  and the second molecule is one or more polypeptides. 
     
     
         7 . The composition as claimed in  claim 6 , characterized in that said chimeric polypeptide contains:
 a polypeptide as claimed in  claim 4 , and   a second polypeptide comprising one or more transcription-regulating sequences and/or one or more translation-regulating sequences.   
     
     
         8 . A method of delivering a molecule to an Otx2 expressing cell in a subject comprising contacting the subject with a polypeptide as claimed in  claim 1 , wherein the polypeptide is bonded to the molecule. 
     
     
         9 . The method as claimed in  claim 8  wherein the method is for diagnostic or therapeutic purposes which enables the specific targeting of the molecule to the Otx2 expressing cells. 
     
     
         10 . The method as claimed in  claim 9 , wherein the molecule is internalized in said Otx2 expressing cells. 
     
     
         11 . (canceled) 
     
     
         12 . A method of increasing the survival of Otx2 expressing cells in a subject comprising administering the composition as claimed in  claim 7  to the subject. 
     
     
         13 . (canceled) 
     
     
         14 . The method as claimed in  claim 8 , wherein said Otx2 expressing cells are retinal ganglion neurons or retinal bipolar neurons. 
     
     
         15 . A method of treating a disease selected from the group consisting of amblyopia, anxiety disorders, post-traumatic stress syndrome, manic depressive psychosis and schizophrenia in a subject in need thereof comprising administering an amount of polypeptide as claimed in  claim 1  which inhibits the binding of Otx2 to parvalbumin neurons to the subject.