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Intestinal transgene delivery with native E. coli chassis allows persistent physiological changes.
Russell, Baylee J; Brown, Steven D; Siguenza, Nicole; Mai, Irene; Saran, Anand R; Lingaraju, Amulya; Maissy, Erica S; Dantas Machado, Ana C; Pinto, Antonio F M; Sanchez, Concepcion; Rossitto, Leigh-Ana; Miyamoto, Yukiko; Richter, R Alexander; Ho, Samuel B; Eckmann, Lars; Hasty, Jeff; Gonzalez, David J; Saghatelian, Alan; Knight, Rob; Zarrinpar, Amir.
Afiliación
  • Russell BJ; Division of Gastroenterology, University of California, San Diego, La Jolla, CA 92093, USA.
  • Brown SD; Division of Gastroenterology, University of California, San Diego, La Jolla, CA 92093, USA.
  • Siguenza N; Division of Gastroenterology, University of California, San Diego, La Jolla, CA 92093, USA.
  • Mai I; Division of Gastroenterology, University of California, San Diego, La Jolla, CA 92093, USA.
  • Saran AR; Division of Gastroenterology, University of California, San Diego, La Jolla, CA 92093, USA.
  • Lingaraju A; Division of Gastroenterology, University of California, San Diego, La Jolla, CA 92093, USA.
  • Maissy ES; Division of Gastroenterology, University of California, San Diego, La Jolla, CA 92093, USA.
  • Dantas Machado AC; Division of Gastroenterology, University of California, San Diego, La Jolla, CA 92093, USA.
  • Pinto AFM; Clayton Foundation Laboratories for Peptide Biology, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
  • Sanchez C; Department of Pharmacology, University of California, San Diego, La Jolla, CA 92093, USA; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92093, USA.
  • Rossitto LA; Department of Pharmacology, University of California, San Diego, La Jolla, CA 92093, USA; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92093, USA.
  • Miyamoto Y; Division of Gastroenterology, University of California, San Diego, La Jolla, CA 92093, USA.
  • Richter RA; Division of Gastroenterology, University of California, San Diego, La Jolla, CA 92093, USA.
  • Ho SB; Division of Gastroenterology, University of California, San Diego, La Jolla, CA 92093, USA; VA Health Sciences San Diego, La Jolla, CA 92161, USA.
  • Eckmann L; Division of Gastroenterology, University of California, San Diego, La Jolla, CA 92093, USA.
  • Hasty J; BioCircuits Institute, University of California, San Diego, La Jolla, CA 92093, USA; Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA; Center for Microbiome Innovation, University of California, San Diego, La Jolla, CA 92093, USA.
  • Gonzalez DJ; Department of Pharmacology, University of California, San Diego, La Jolla, CA 92093, USA; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92093, USA; Center for Microbiome Innovation, University of California, San Diego, La Jolla, CA 92093, US
  • Saghatelian A; Clayton Foundation Laboratories for Peptide Biology, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
  • Knight R; Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA; Department of Pediatrics, University of California, San Diego, La Jolla, CA 92093, USA; Center for Microbiome Innovation, University of California, San Diego, La Jolla, CA 92093, USA; Department of Computer S
  • Zarrinpar A; Division of Gastroenterology, University of California, San Diego, La Jolla, CA 92093, USA; VA Health Sciences San Diego, La Jolla, CA 92161, USA; Center for Microbiome Innovation, University of California, San Diego, La Jolla, CA 92093, USA. Electronic address: azarrinpar@ucsd.edu.
Cell ; 185(17): 3263-3277.e15, 2022 08 18.
Article en En | MEDLINE | ID: mdl-35931082
ABSTRACT
Live bacterial therapeutics (LBTs) could reverse diseases by engrafting in the gut and providing persistent beneficial functions in the host. However, attempts to functionally manipulate the gut microbiome of conventionally raised (CR) hosts have been unsuccessful because engineered microbial organisms (i.e., chassis) have difficulty in colonizing the hostile luminal environment. In this proof-of-concept study, we use native bacteria as chassis for transgene delivery to impact CR host physiology. Native Escherichia coli bacteria isolated from the stool cultures of CR mice were modified to express functional genes. The reintroduction of these strains induces perpetual engraftment in the intestine. In addition, engineered native E. coli can induce functional changes that affect physiology of and reverse pathology in CR hosts months after administration. Thus, using native bacteria as chassis to "knock in" specific functions allows mechanistic studies of specific microbial activities in the microbiome of CR hosts and enables LBT with curative intent.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Contexto en salud: 3_ND Problema de salud: 3_neglected_diseases / 3_zoonosis Asunto principal: Microbiota / Microbioma Gastrointestinal Límite: Animals Idioma: En Revista: Cell Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Contexto en salud: 3_ND Problema de salud: 3_neglected_diseases / 3_zoonosis Asunto principal: Microbiota / Microbioma Gastrointestinal Límite: Animals Idioma: En Revista: Cell Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos