A novel peptide, PLAEIDGIELTY, for the targeting of α 9 β 1 ‐integrins

Targeting gene therapy vectors to abundant receptors on airway epithelia may allow a significant enhancement of gene delivery and thereby be of particular importance for the gene therapy of cystic fibrosis. α 9 β 1 ‐Integrins are highly expressed throughout the human airway epithelia in vivo, irrespective of any particular clinical status. Aiming to improve the targeting of our non‐viral integrin‐mediated gene transfer systems to airway epithelia, we searched for a short tenascin C‐derived peptide which would bind to these integrins. By utilizing recombinant bacteriophages that display overlapping regions of the third fibronectin type III repeat of tenascin C (TNfn3), we were able to localize its α 9 β 1 ‐integrin binding site to the B‐C loop of TNfn3. A synthetic Pro‐Leu‐Ala‐Glu‐Ile‐Asp‐Gly‐Ile‐Glu‐Leu‐Thr‐Tyr peptide (PLAEIDGIELTY) was shown to displace α 9 β 1 ‐integrin‐expressing cells completely from binding to TNfn3. This peptide, therefore, may prove useful both for the examination of the functional importance of α 9 β 1 ‐integrins in vivo and the development of gene therapy vectors or drugs targeting these integrins.