MUTATED ADENO-ASSOCIATED VIRUS CAPSID PROTEINS, AAV PARTICLE COMPRISING THE SAME AND LIVER DIRECTED AAV VECTOR GENE THERAPY

摘要

The present invention relates in a first aspect to a mutated adeno-associated virus (AAV) capsid protein or fragment thereof having an insert composed of an oligopeptide optionally having further amino acids representing linker sequences flanking both sites of said oligopeptide. These mutated AAV capsid proteins are more efficient in targeting hepatic tissue, hepatocytes, hepatic cells and cell lines or hepatocellular carcinoma (HCC) with partially higher specificity. Further, a mutated AAV particle comprising the mutated AAV capsid protein according to the present invention is provided. In addition, a nucleic acid encoding the mutated AAV capsid protein according to the present invention is identified together with a corresponding nucleic acid vector, in particular, a plasmid. In addition, a host cell containing the nucleic acid vector or the nucleic acid molecule according to the present invention. Further, a use of the AAV particle or the nucleic acid or the nucleic acid vector according to the present invention in the manufacture of an AAV particle, or in the manufacture of a medicament for gene therapy is described. Moreover, the described protein, particle molecules as well as nucleic acid vectors for use in targeting hepatocytes and/or HCC are de- scribed. In particular, said components for use in treating diseases involving hepatocytes or for treating HCC are disclosed, in particular, for use in gene therapy, e.g. for use in a transfer of a gene of interest into hepatocytes, heptatic tissue or HCC.