Methods and compositions for targeting proteins across the blood brain barrier

Abstract

Disclosed are methods and compositions for targeting therapeutic proteins to the brain. Methods and compositions of the invention involve associating an IGF moiety with a therapeutic protein in order to target the therapeutic protein to the brain. Soluble fusion proteins that include an IGF targeting moiety are transported to neural tissue in the brain from blood. Methods and compositions of the invention include therapeutic applications for treating lysosomal storage diseases. The invention also provides nucleic acids and cells for expressing IGF fusion proteins.

1 . A method for targeting a polypeptide to the brain, the method comprising the step of providing a polypeptide in association with an IGF moiety to a mammal, thereby resulting in accumulation of the polypeptide in the brain of said mammal.  
     
     
         2 . A method for producing a CNS-targeted polypeptide, the method comprising the step of expressing a polypeptide in association with an IGF moiety, thereby to produce a polypeptide with a CNS-targeting tag.  
     
     
         3 . A composition comprising a polypeptide in association with an IGF moiety, wherein said IGF moiety targets the composition to the brain.  
     
     
         4 . The composition of  claim 3  wherein said polypeptide and IGF moiety are expressed as a fusion protein.  
     
     
         5 . The method of  claim 1  or  2 , wherein said IGF moiety is an IGF-I targeting moiety.  
     
     
         6 . The composition of  claim 3  or  4 , wherein said IGF moiety is an IGF-I targeting moiety.