Adhesion receptors mediate efficient non-viral gene delivery.
For a variety of reasons, including production limitations, potential unanticipated side effects, and an immunological response upon repeated systemic administration, virus-based vectors are as yet not ideal gene delivery vehicles, justifying further research into alternatives. Unlike viral vectors, non-viral vectors pose minimal health risks, but to meet therapeutic requirements their efficacy needs major improvement. This goal may be accomplished by better defining the mechanism of non-viral gene delivery and exploiting specific cellular properties. Here we demonstrate that transfection of epithelial cells with lipoplexes is almost exclusively mediated by the beta1 integrin cell surface receptor. More important, we show that in general, adhesion receptors can be exploited by lipoplexes to gain access to cells, including difficult-to-transfect primary neural stem cells and suspension cells, thereby leading to productive transfection. We propose that adhesion receptors serve as "natural" receptors for lipoplexes. As no natural cellular receptors for lipoplexes have previously been identified, our results are an important step forward in understanding the mechanisms of non-viral gene delivery. Moreover, the finding that adhesion receptors mediate efficient non-viral gene delivery paves the way for the optimization of (standard) transfection procedures as well as ex vivo gene therapy protocols using non-viral vectors.
Zuhorn
Inge S
IS
Biomade Technology Foundation, Nijenborgh, Groningen, The Netherlands. i.zuhorn@med.umcg.nl
Kalicharan
Dharamdajal
D
Robillard
George T
GT
Hoekstra
Dick
D
D000818:Animals; D002450:Cell Communication / Q000187:drug effects; D002460:Cell Line; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D004533:Egtazic Acid / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D005786:Gene Expression Regulation / Q000187:drug effects; D005822:Genetic Vectors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D047468:Immunoprecipitation; D019012:Integrin beta1 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D007797:Laminin / Q000494:pharmacology; D008081:Liposomes; D008562:Membrane Glycoproteins; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D046529:Microscopy, Electron, Transmission; D009474:Neurons / Q000166:cytology; D010703:Phorbol Esters / Q000494:pharmacology; D019038:Platelet Glycoprotein GPIb-IX Complex; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000235:genetics; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D014162:Transfection / Q000379:methods*
D019012:Integrin beta1; D007797:Laminin; D008081:Liposomes; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D010703:Phorbol Esters; D019038:Platelet Glycoprotein GPIb-IX Complex; D034741:RNA, Small Interfering; C094990:adhesion receptor; D049452:Green Fluorescent Proteins; D004533:Egtazic Acid