Polymyxin B Treatment Improves Bactofection Efficacy and Reduces Cytotoxicity
Autor: | Charles H. Jones, Snehal Rane, Chih-Kuang Chen, Anitha Ravikrishnan, Emily Patt, Blaine A. Pfeifer, Chong Cheng |
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Jazyk: | angličtina |
Rok vydání: | 2013 |
Předmět: |
Genetic enhancement
Bacterial Toxins Pharmaceutical Science Pharmacology Gene delivery medicine.disease_cause Article Cell Line Hemolysin Proteins Mice Drug Discovery medicine Escherichia coli Animals Humans Cytotoxicity Heat-Shock Proteins Polymyxin B Chemistry fungi food and beverages Transfection Genetic Therapy Molecular Medicine medicine.drug |
Popis: | Improvements to bacterial vectors have resulted in non-viral gene therapy vehicles that are easily prepared and can achieve high levels of transfection efficacy. However, these vectors are plagued by potential cytotoxicity and immunogenicity, prompting means of attenuation to reduce unwanted biological outcomes while maintaining transfection efficiency. In this study, listeriolysin O (LLO) producing Escherichia coli BL21(DE3) strains were pre-treated with polymyxin B (PLB), a pore-forming antibiotic, and tested as a delivery vector for gene transfer to a murine RAW264.7 macrophage cell line using a 96-well high-throughput assay. PLB treatment resulted in statistically significant higher levels of gene delivery and lower cytotoxicity. The results suggest a fine balance between bacterial cellular damage, heightened gene and protein release, and increased mammalian cell gene delivery. Overall, the approach presented provides a simple and effective way to enhance bacterial gene delivery while simultaneously reducing unwanted outcomes as a function of using a biological vector. |
Databáze: | OpenAIRE |
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