Attenuated Shigella as a DNA Delivery Vehicle for DNA-Mediated Immunization

• Published in: Science (American Association for the Advancement of Science) Vol. 270; no. 5234; pp. 299 - 302
• Main Authors: Sizemore, Donata R., Branstrom, Arthur A., Sadoff, Jerald C.
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society for the Advancement of Science 13.10.1995; American Association for the Advancement of Science; The American Association for the Advancement of Science
• Subjects: Animals; Applied microbiology; Autism; Autism Spectrum Disorders; Bacteria; Bacterial vaccines; Base Sequence; beta-Galactosidase - biosynthesis; beta-Galactosidase - genetics; Biological and medical sciences; Biotechnology; Cell Line; Cellular immunity; Cornea; Cricetinae; Cytoplasm; Delivery Systems; Deoxyribonucleic acid; DNA; DNA - genetics; Epithelial cells; Fundamental and applied biological sciences. Psychology; Gene Expression; Gene therapy; Gene Transfer Techniques; Genes; Genetic Therapy; Genetic Vectors; Guinea Pigs; Health. Pharmaceutical industry; Immunization; Industrial applications and implications. Economical aspects; Mice; Microbiology; Molecular Sequence Data; Plasmids; Production of active biomolecules; Shigella; Shigella flexneri - genetics; Shigella flexneri - pathogenicity; Shigella flexneri - physiology; Spleen cells; Vaccination; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Vaccins; Plasmid; Vertebrata; Immunization; Mammalia; DNA; Bacteria; Host; Vaccine; Attenuated strain; Vector; Shigella; Enterobacteriaceae
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.270.5234.299

Direct inoculation of DNA, in the form of purified bacterial plasmids that are unable to replicate in mammalian cells but are able to direct cell synthesis of foreign proteins, is being explored as an approach to vaccine development. Here, a highly attenuated Shigella vector invaded mammalian cells and delivered such plasmids into the cytoplasm of cells, and subsequent production of functional foreign protein was measured. Because this Shigella vector was designed to deliver DNA to colonic mucosa, the method is a potential basis for oral and other mucosal DNA immunization and gene therapy strategies.