A programmable encapsulation system improves delivery of therapeutic bacteria in mice

Living bacteria therapies have been proposed as an alternative approach to treating a broad array of cancers. In this study, we developed a genetically encoded microbial encapsulation system with tunable and dynamic expression of surface capsular polysaccharides that enhances systemic delivery. Based on a small RNA screen of capsular biosynthesis pathways, we constructed inducible synthetic gene circuits that regulate bacterial encapsulation in Escherichia coli Nissle 1917. These bacteria are capable of temporarily evading immune attack, whereas subsequent loss of encapsulation results in effective clearance in vivo. This dynamic delivery strategy enabled a ten-fold increase in maximum tolerated dose of…

• UD
  U.S. Department of Defense

  Awards: BC160541, LC160314
• HI
  Honjo International Scholarship Foundation
• NI
  National Institutes of Health

  Award: U01CA247573
• NC
  National Cancer Institute

  Awards: U01CA247573, R01CA249160, F99CA253756