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

Abstract

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.