Targeted protein replacement for the treatment of lysosomal storage disorders

Abstract

The present invention relates to compositions and methods for delivering lysosomal proteins. The compositions and methods described herein permit the targeted delivery of exogenous lysosomal proteins to cell surface proteins that allow their internalization via non-clathrin pathways. The present invention further relates to the use of the compositions and methods for enzyme replacement therapy of lysosomal storage diseases. Nucleic acids, recombinant cells and kits useful for making and using the compositions of the invention are also provided.

1 .- 36 . (canceled) 
     
     
         37 . A nucleic acid comprising a nucleotide sequence encoding a mammalian lysosomal protein or active fragment thereof which is attached to a targeting moiety, wherein the targeting moiety binds to a mammalian cell surface molecule and allows internalization of said mammalian lysosomal protein or active fragment by the mammalian cell via a non-clathrin pathway, wherein the mammalian lysosomal protein or active fragment is covalently attached to said targeting moiety and said protein or said fragment, and wherein the mammalian lysosomal protein or active fragment is a fusion protein comprising said targeting moiety and said protein or said fragment. 
     
     
         38 . The nucleic acid of  claim 37  in which the nucleotide sequence is operably linked to a promoter. 
     
     
         39 .- 44 . (canceled) 
     
     
         45 . A nucleic acid comprising a nucleotide sequence encoding a mammalian lysosomal protein or active fragment thereof which is attached to a targeting moiety, wherein the targeting moiety binds to a mammalian cell surface molecule and allows internalization of said mammalian lysosomal protein or active fragment by the mammalian cell via a non-clathrin pathway, wherein the mammalian lysosomal protein or active fragment is covalently attached to said targeting moiety and said protein or said fragment, and wherein the mammalian lysosomal protein or active fragment is a fusion protein comprising said targeting moiety and said protein or said fragment, and in which the targeting moiety is N-terminal to said protein or said fragment. 
     
     
         46 . The nucleic acid of  claim 45  in which the nucleotide sequence is operably linked to a promoter. 
     
     
         47 . A nucleic acid comprising a nucleotide sequence encoding a mammalian lysosomal protein or active fragment thereof which is attached to a targeting moiety, wherein the targeting moiety binds to a mammalian cell surface molecule and allows internalization of said mammalian lysosomal protein or active fragment by the mammalian cell via a non-clathrin pathway, wherein the mammalian lysosomal protein or active fragment is covalently attached to said targeting moiety and said protein or said fragment, and wherein the mammalian lysosomal protein or active fragment is a fusion protein comprising said targeting moiety and said protein or said fragment, and in which the targeting moiety is C-terminal to said protein or said fragment. 
     
     
         48 . The nucleic acid of  claim 47  in which the nucleotide sequence is operably linked to a promoter.