title: Engineering of Escherichia coli for targeted delivery of transgenes to HER2/neu-positive tumor cells.
abstract: Targeting of non-phagocytic tumor cells and prompt release of gene cargos upon entry into tumors are two limiting steps in the bacterial gene delivery path. To tackle these problems, the non-pathogenic Escherichia coli strain BL21(DE3) was engineered to display the anti-HER2/neu affibody on the surface. After co-incubation with tumor cells for 3 h, the anti-HER2/neu affibody-presenting E. coli strain was selectively internalized into HER2/neu-positive SKBR-3 cells. The invasion efficiency reached as high as 30%. Furthermore, the bacteria were equipped with the phage ϕX174 lysin gene E-mediated autolysis system. Carrying the transgene (e.g., eukaryotic green fluorescent protein, GFP), the tumor-targeting bacteria were subjected to the thermal shock to trigger the autolysis system upon entry into HER2/neu-positive cells. Flow cytometric analysis revealed that 3% of infected cells expressed GFP 24 h post thermal induction. Overall, the results show a promise of the proposed approach for developing bacteria as a delivery carrier.
authors.affiliation: Department of Chemical Engineering, Feng Chia University, 100 Wenhwa Road, Taichung 40724, Taiwan.
authors.forename: Chih-Hsiang
authors.initials: CH
authors.lastname: Chang
authors.forename: Wei-Jou
authors.initials: WJ
authors.lastname: Cheng
authors.forename: Shan-Yu
authors.initials: SY
authors.lastname: Chen
authors.forename: Ming-Ching
authors.initials: MC
authors.lastname: Kao
authors.forename: Chung-Jen
authors.initials: CJ
authors.lastname: Chiang
authors.forename: Yun-Peng
authors.initials: YP
authors.lastname: Chao
mesh_terms: D000906:Antibodies / Q000276:immunology / Q000378:metabolism; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D004926:Escherichia coli / Q000235:genetics* / Q000502:physiology*; D018014:Gene Transfer Techniques; D022761:Gene Transfer, Horizontal; D006801:Humans; D011485:Protein Binding; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology / Q000378:metabolism; D019076:Transgenes
chemical_list: D000906:Antibodies; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human