Targeted gene delivery into α9β1‐integrin‐displaying cells by a synthetic peptide

FEBS Letters

Harbottle, Richard P.¹  Jost, Philipp¹  Schneider, Holm¹  Coutelle, Charles¹  Yokosaki, Yasuyuki² 

[1] Cystic Fibrosis Gene Therapy Research Group, Section of Molecular Genetics, Division of Biomedical Sciences, Imperial College School of Medicine, Sir Alexander Fleming Building, London SW7 2AZ, UK;Department of Laboratory Medicine, National Hiroshima Hospital, 513 Jike, Saijoh, Higashi-Hiroshima 739-0041, Japan

关键词: α9β1-Integrin;    DNA transfer;    Peptide;    Receptor-mediated;    Gene therapy;    TNfn3;    third fibronectin type III repeat of tenascin C;    DMEM;    Dulbecco's modified Eagle's medium;    PBS;    phosphate-buffered saline;    BSA;    bovine serum albumin;    FCS;    foetal calf serum;   

DOI  :  10.1016/S0014-5793(99)01181-3

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

We have investigated the usefulness of two small synthetic peptides comprising either a linear or a cyclic PLAEIDGIEL domain and a DNA-binding moiety of 16 lysine residues to mediate gene transfer selectively into α₉β₁-integrin-displaying cells. Such specific gene delivery could only be achieved with the peptide containing the cyclic PLAEIDGIEL domain. However, inclusion of the cationic liposome LipofectAMINE into the peptide/DNA complexes resulted for both peptides in efficient gene transfer with significant targeting specificity. Naturally, the integrin α₉β₁ is present only in a few highly specialised tissues and abundant throughout the human airway epithelia in vivo. Targeting gene vectors to this integrin therefore appears a useful approach to gene therapy of lung diseases such as cystic fibrosis. As the integrin α₉β₁ is associated with tissue differentiation during foetal development and may cause resurgence of the foetal phenotype in colon cancers, such vectors may also be applicable for prenatal and cancer gene therapy.

【 授权许可】

Unknown