A programmable encapsulation system improves delivery of therapeutic bacteria in mice
Abstract
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 bacteria and improved anti-tumor efficacy in murine models of cancer. Furthermore, in situ encapsulation increased the fraction of microbial translocation among mouse tumors, leading to efficacy in distal tumors. The programmable encapsulation system promises to enhance the therapeutic utility of living engineered bacteria for cancer.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Mar 17, 2022
- Source ID
- 10.1038/s41587-022-01244-y
Entities
People
- Clare Nimura
- Courtney Coker
- Fangda Li
- Jaeseung Hahn
- Joanna Zhang
- Jongwon Im
- Kam W. Leong
- Kelly Pu
- Kelsey Gray
- Nicholas Arpaia
- Nicholas Hou
- Nicole Harr
- Sreyan Chowdhury
- Tal Danino
- Tetsuhiro Harimoto
- Yu-yu Chen
Organizations
- Honjo International Scholarship Foundation
- National Cancer Institute
- United States Department of Defense