Abstract
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. Alpha9beta1-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 alpha9beta1-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 alpha9beta1-integrin-expressing cells completely from binding to TNfn3. This peptide, therefore, may prove useful both for the examination of the functional importance of alpha9beta1-integrins in vivo and the development of gene therapy vectors or drugs targeting these integrins.
References
Nov 6, 1992·Science·D J LeahyH P Erickson
May 1, 1992·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·P Van EykenV J Desmet
Apr 3, 1992·Cell·R O Hynes
Jan 1, 1990·Ophthalmic Research·T TervoI Virtanen
Aug 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·S E CwirlaW J Dower
Dec 6, 1990·Nature·J McCaffertyD J Chiswell
Feb 1, 1994·The Journal of Cell Biology·E KoivunenE Ruoslahti
Oct 27, 1994·Nature·B R GrubbR C Boucher
May 1, 1995·American Journal of Respiratory Cell and Molecular Biology·A WeinackerD Sheppard
Oct 1, 1995·Journal of Virology·M J Goldman, J M Wilson
Aug 1, 1993·American Journal of Clinical Pathology·Y SoiniV P Lehto
Nov 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·A L PrietoK L Crossin
Apr 23, 1993·Cell·T J WickhamG R Nemerow
Mar 1, 1996·Chest·D Sheppard, Y Yokosaki
Mar 1, 1996·Nature Medicine·M A BarryS A Johnston
Nov 8, 1996·The Journal of Biological Chemistry·L L SmithC M Giachelli
Sep 1, 1997·The Journal of Clinical Investigation·J ZabnerM J Welsh
Jun 2, 1998·Human Gene Therapy·R P HarbottleC Coutelle
Jun 6, 1998·Gene Therapy·K TakayamaN Hara
Citations
Dec 10, 1999·Analytical Biochemistry·S C ChiuC H Lu
Nov 10, 2000·Advanced Drug Delivery Reviews·R J Parkes, S L Hart
Dec 6, 2001·Advanced Drug Delivery Reviews·C PichonP Midoux
Jan 25, 2002·Medicine·Danuta Balicki, Ernest Beutler
Apr 6, 2007·The AAPS Journal·Molly E Martin, Kevin G Rice
Dec 23, 2008·Journal of Controlled Release : Official Journal of the Controlled Release Society·Wing-Fu Lai, Marie Chia-Mi Lin
Apr 20, 1999·The Journal of Cell Biology·Y TaookaD Sheppard
Nov 26, 1999·FEBS Letters·H SchneiderC Coutelle
Jun 7, 2005·Chembiochem : a European Journal of Chemical Biology·Jodie E WaterhouseAndrew D Miller
Feb 13, 2001·FEBS Letters·P J JostH Schneider
Jun 26, 2003·The Journal of Biological Chemistry·Michael StefanidakisErkki Koivunen
Oct 13, 2000·Breast Cancer : the Journal of the Japanese Breast Cancer Society·K ArihiroY Yokosaki
Jul 28, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Motomichi FujitaFumio Fukai
Mar 18, 2020·MedChemComm·A GiganteC Schmuck
Sep 10, 2008·Human Gene Therapy·April F WhiteSelvarangan Ponnazhagan
Apr 11, 2000·Journal of Pharmaceutical Sciences·U Wojda, J L Miller
Aug 24, 2010·Matrix Biology : Journal of the International Society for Matrix Biology·Helge WiigRaghu Kalluri