Peptides having specificity for the lungs

Abstract

The invention relates to a peptide, polypeptide, or protein that binds specifically to cells of the lung endothelium. The peptide, polypeptide, or protein can be a component of a viral capsid and can be used to lead a recombinant viral vector selectively to the lung endothelial tissue after systemic administration to a subject and to ensure tissue-specific expression of one or more transgenes there. The invention thus further relates to a recombinant viral vector, preferably an AAV vector, which comprises a capsid comprising the peptide, polypeptide, or protein according to the invention and which comprises at least one transgene packaged in the capsid. The viral vector is suitable in particular for the therapeutic treatment of a lung disorder or a lung disease. The invention further relates to cells and pharmaceutical compositions which comprise the viral vector according to the invention.

1 . A peptide, polypeptide, or protein that specifically binds to cells of the lung, characterized in that it comprises the amino acid sequence of SEQ ID NO: 1. 
     
     
         2 . The peptide, polypeptide, or protein according to  claim 1 , which has the amino acid sequence of SEQ ID NO: 2, or a variant thereof which differs from the amino acid sequence of SEQ ID NO: 2 by a modification of at least one of the two N-terminal amino acids. 
     
     
         3 . The protein according to  claim 1 , which is a capsid protein of a viral vector. 
     
     
         4 . The protein according to  claim 3 , which is a capsid protein of an adeno-associated virus (AAV). 
     
     
         5 . The protein according to  claim 4 , which is a capsid protein of an AAV of a serotype selected from the group consisting of serotypes 2, 4, 6, 8, and 9, preferably serotype 2. 
     
     
         6 . The protein according to  claim 5 , which is a VP1 protein of an AAV of serotype 2. 
     
     
         7 . The protein according to  claim 1 , comprising the following:
 (a) the amino acid sequence of SEQ ID NO: 9;   (b) an amino acid sequence having at least 80% identity to the amino acid sequence of SEQ ID NO: 9; or   (c) a fragment of one of the amino acid sequences defined in (a) or (b).   
     
     
         8 . A viral capsid which comprises a peptide, polypeptide, or protein according to  claim 1 . 
     
     
         9 . A nucleic acid which encodes a peptide, polypeptide, or protein according to  claim 1 . 
     
     
         10 . A plasmid which comprises a nucleic acid according to  claim 9 . 
     
     
         11 . A recombinant viral vector which comprises a capsid and a transgene packaged therein, wherein the capsid comprises at least one capsid protein having the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a variant thereof which differs from the amino acid sequence of SEQ ID NO: 2 by modification of at least one of the two N-terminal amino acids. 
     
     
         12 . The recombinant viral vector according to  claim 11 , which is a recombinant AAV vector. 
     
     
         13 . The recombinant AAV vector according to  claim 12 , which is an AAV vector of a serotype selected from the group consisting of serotypes 2, 4, 6, 8, and 9. 
     
     
         14 . The recombinant AAV vector according to  claim 11 , wherein the transgene encodes a nitric oxide synthase, bone morphogenic protein receptor 2 (BMPR2), endothelial nitric oxide synthase (eNOS), or inducible nitric oxide synthase (iNOS). 
     
     
         15 . The recombinant AAV vector according to  claim 11 , wherein the transgene is in the form of an ssDNA or a dsDNA. 
     
     
         16 . The recombinant AAV vector according to  claim 11 , for use in a method for the treatment of a lung disorder or a lung disease in a subject. 
     
     
         17 . The recombinant AAV vector for use in a method according to  claim 16 , wherein the lung disease is pulmonary hypertension or pulmonary arterial hypertension. 
     
     
         18 . The recombinant AAV vector for use in a method according to  claim 16 , wherein the subject is a mammal, preferably a human. 
     
     
         19 . A cell which comprises a peptide, polypeptide, or protein according to  claim 1 . 
     
     
         20 . A pharmaceutical composition which comprises a peptide, polypeptide, or protein according to  claim 1 .