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A programmable encapsulation system improves delivery of therapeutic bacteria in mice.
Harimoto, Tetsuhiro; Hahn, Jaeseung; Chen, Yu-Yu; Im, Jongwon; Zhang, Joanna; Hou, Nicholas; Li, Fangda; Coker, Courtney; Gray, Kelsey; Harr, Nicole; Chowdhury, Sreyan; Pu, Kelly; Nimura, Clare; Arpaia, Nicholas; Leong, Kam W; Danino, Tal.
Afiliação
  • Harimoto T; Department of Biomedical Engineering, Columbia University, New York, NY, USA.
  • Hahn J; Department of Biomedical Engineering, Columbia University, New York, NY, USA.
  • Chen YY; Department of Biomedical Engineering, Columbia University, New York, NY, USA.
  • Im J; Department of Biomedical Engineering, Columbia University, New York, NY, USA.
  • Zhang J; Department of Biomedical Engineering, Columbia University, New York, NY, USA.
  • Hou N; Department of Biomedical Engineering, Columbia University, New York, NY, USA.
  • Li F; Department of Microbiology and Immunology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA.
  • Coker C; Department of Biomedical Engineering, Columbia University, New York, NY, USA.
  • Gray K; Department of Biomedical Engineering, Columbia University, New York, NY, USA.
  • Harr N; Department of Biomedical Engineering, Columbia University, New York, NY, USA.
  • Chowdhury S; Department of Biomedical Engineering, Columbia University, New York, NY, USA.
  • Pu K; Department of Microbiology and Immunology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA.
  • Nimura C; Department of Biomedical Engineering, Columbia University, New York, NY, USA.
  • Arpaia N; Department of Biomedical Engineering, Columbia University, New York, NY, USA.
  • Leong KW; Department of Microbiology and Immunology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA.
  • Danino T; Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY, USA.
Nat Biotechnol ; 40(8): 1259-1269, 2022 08.
Article em En | MEDLINE | ID: mdl-35301496
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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Escherichia coli / Neoplasias Limite: Animals Idioma: En Revista: Nat Biotechnol Assunto da revista: BIOTECNOLOGIA Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Escherichia coli / Neoplasias Limite: Animals Idioma: En Revista: Nat Biotechnol Assunto da revista: BIOTECNOLOGIA Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Estados Unidos