Transgene delivering retrovirus targeting collagen exposed at site of tissue injury
A viral or non-viral vector particle having a modified viral surface protein wherein the viral surface protein is modified to include a targeting polypeptide including a binding region which binds to an extracellular matrix component. Such vector particles are useful in delivering genes encoding therapeutic agents to cells located at the site of an exposed extracellular matrix component.
1. A recombinant modified polynucleotide encoding a modified viral envelope protein for targeting a viral vector to an extracellular matrix, wherein the modified viral envelope protein includes a targeting polypeptide comprising a binding region which binds to collagen.
2. The recombinant modified polynucleotide of claim 1 , wherein said modified viral envelope protein is a modified retroviral envelope protein.
3. The recombinant modified polynucleotide of claim 2 , wherein said modified retroviral envelope protein comprises a modified receptor binding region comprising said targeting polypeptide.
4. The recombinant modified polynucleotide of claim 3 , wherein said modified receptor binding region has the sequence set forth in SEQ ID NO:1 which additionally comprises said targeting polypeptide inserted between amino acid residues 18 and 19 of SEQ ID NO:1.
5. The recombinant modified polynucleotide of claim 1 , wherein the collagen is collagen Type I or collagen Type IV.
6. The recombinant polynucleotide of claim 4 , wherein the binding region of the targeting polypeptide encodes the sequence Trp-Arg-Glu-Pro-Ser-Phe-Met-Ala-Leu-Ser (SEQ ID NO:3).
7. A producer cell for producing retroviral vector particles having a modified envelope protein, said producer cell including the recombinant modified polynucleotide of claim 2 .