Bacterial spores as particulate carriers for gene gun delivery of plasmid DNA

J Biotechnol. 2016 Jun 20:228:58-66. doi: 10.1016/j.jbiotec.2016.04.027. Epub 2016 Apr 27.

Abstract

Bacillus subtilis spores represent a suitable platform for the adsorption of proteins, enzymes and viral particles at physiological conditions. In the present work, we demonstrate that purified spores can also adsorb DNA on their surface after treatment with cationic molecules. In addition, we demonstrate that DNA-coated B. subtilis spores can be used as particulate carriers and act as an alternative to gold microparticles for the biolistic (gene gun) administration of plasmid DNA in mice. Gene gun delivery of spores pre-treated with DODAB (dioctadecyldimethylammonium bromide) allowed efficient plasmid DNA absorption and induced protein expression levels similar to those obtained with gold microparticles. More importantly, we demonstrated that a DNA vaccine adsorbed on spores can be loaded into biolistic cartridges and efficiently delivered into mice, which induced specific cellular and antibody responses. Altogether, these data indicate that B. subtilis spores represent a simple and low cost alternative for the in vivo delivery of DNA vaccines by the gene gun technology.

Keywords: Adsorption; Biolistic; DNA vaccine; Gene gun; Spores.

MeSH terms

  • Adsorption
  • Animals
  • Bacillus subtilis / chemistry
  • Biolistics / methods*
  • Drug Carriers / administration & dosage
  • Drug Carriers / chemistry*
  • Gold / chemistry
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Oncogene Proteins, Viral / genetics
  • Oncogene Proteins, Viral / immunology
  • Quaternary Ammonium Compounds / chemistry
  • Spores, Bacterial / chemistry*
  • Spores, Bacterial / immunology
  • Vaccines, DNA / administration & dosage
  • Vaccines, DNA / chemistry*
  • Vaccines, DNA / immunology

Substances

  • Drug Carriers
  • Oncogene Proteins, Viral
  • Quaternary Ammonium Compounds
  • Vaccines, DNA
  • dimethyldioctadecylammonium
  • Gold