Novel Strategies for Efficient Production and Delivery of Live Biotherapeutics and Biotechnological Uses of Lactococcus lactis: The Lactic Acid Bacterium Model

Lactic acid bacteria (LAB) are traditionally used in fermentation and food preservation processes and are recognized as safe for consumption. Recently, they have attracted attention due to their health-promoting properties; many species are already widely used as probiotics for treatment or preventi...

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Main Authors: Laísa M. Tavares, Luís C. L. de Jesus, Tales F. da Silva, Fernanda A. L. Barroso, Viviane L. Batista, Nina D. Coelho-Rocha, Vasco Azevedo, Mariana M. Drumond, Pamela Mancha-Agresti
Format: Article
Language:English
Published: Frontiers Media S.A. 2020-11-01
Series:Frontiers in Bioengineering and Biotechnology
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Online Access:https://www.frontiersin.org/articles/10.3389/fbioe.2020.517166/full
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spelling doaj-d614e873d95f4112be2fa4e5b2e79c0d2020-11-25T03:04:04ZengFrontiers Media S.A.Frontiers in Bioengineering and Biotechnology2296-41852020-11-01810.3389/fbioe.2020.517166517166Novel Strategies for Efficient Production and Delivery of Live Biotherapeutics and Biotechnological Uses of Lactococcus lactis: The Lactic Acid Bacterium ModelLaísa M. Tavares0Luís C. L. de Jesus1Tales F. da Silva2Fernanda A. L. Barroso3Viviane L. Batista4Nina D. Coelho-Rocha5Vasco Azevedo6Mariana M. Drumond7Mariana M. Drumond8Pamela Mancha-Agresti9Pamela Mancha-Agresti10Laboratory of Cellular and Molecular Genetics, Federal University of Minas Gerais, Belo Horizonte, BrazilLaboratory of Cellular and Molecular Genetics, Federal University of Minas Gerais, Belo Horizonte, BrazilLaboratory of Cellular and Molecular Genetics, Federal University of Minas Gerais, Belo Horizonte, BrazilLaboratory of Cellular and Molecular Genetics, Federal University of Minas Gerais, Belo Horizonte, BrazilLaboratory of Cellular and Molecular Genetics, Federal University of Minas Gerais, Belo Horizonte, BrazilLaboratory of Cellular and Molecular Genetics, Federal University of Minas Gerais, Belo Horizonte, BrazilLaboratory of Cellular and Molecular Genetics, Federal University of Minas Gerais, Belo Horizonte, BrazilLaboratory of Cellular and Molecular Genetics, Federal University of Minas Gerais, Belo Horizonte, BrazilDepartamento de Ciências Biológicas, Centro Federal de Educação Tecnológica de Minas Gerais, Belo Horizonte, BrazilLaboratory of Cellular and Molecular Genetics, Federal University of Minas Gerais, Belo Horizonte, BrazilFAMINAS - BH, Belo Horizonte, BrazilLactic acid bacteria (LAB) are traditionally used in fermentation and food preservation processes and are recognized as safe for consumption. Recently, they have attracted attention due to their health-promoting properties; many species are already widely used as probiotics for treatment or prevention of various medical conditions, including inflammatory bowel diseases, infections, and autoimmune disorders. Some LAB, especially Lactococcus lactis, have been engineered as live vehicles for delivery of DNA vaccines and for production of therapeutic biomolecules. Here, we summarize work on engineering of LAB, with emphasis on the model LAB, L. lactis. We review the various expression systems for the production of heterologous proteins in Lactococcus spp. and its use as a live delivery system of DNA vaccines and for expression of biotherapeutics using the eukaryotic cell machinery. We have included examples of molecules produced by these expression platforms and their application in clinical disorders. We also present the CRISPR-Cas approach as a novel methodology for the development and optimization of food-grade expression of useful substances, and detail methods to improve DNA delivery by LAB to the gastrointestinal tract. Finally, we discuss perspectives for the development of medical applications of recombinant LABs involving animal model studies and human clinical trials, and we touch on the main safety issues that need to be taken into account so that bioengineered versions of these generally recognized as safe organisms will be considered acceptable for medical use.https://www.frontiersin.org/articles/10.3389/fbioe.2020.517166/fullLactococcus lactisgenetic engineeringbiotherapeutic moleculesmucosal immunitysafe for consumption
collection DOAJ
language English
format Article
sources DOAJ
author Laísa M. Tavares
Luís C. L. de Jesus
Tales F. da Silva
Fernanda A. L. Barroso
Viviane L. Batista
Nina D. Coelho-Rocha
Vasco Azevedo
Mariana M. Drumond
Mariana M. Drumond
Pamela Mancha-Agresti
Pamela Mancha-Agresti
spellingShingle Laísa M. Tavares
Luís C. L. de Jesus
Tales F. da Silva
Fernanda A. L. Barroso
Viviane L. Batista
Nina D. Coelho-Rocha
Vasco Azevedo
Mariana M. Drumond
Mariana M. Drumond
Pamela Mancha-Agresti
Pamela Mancha-Agresti
Novel Strategies for Efficient Production and Delivery of Live Biotherapeutics and Biotechnological Uses of Lactococcus lactis: The Lactic Acid Bacterium Model
Frontiers in Bioengineering and Biotechnology
Lactococcus lactis
genetic engineering
biotherapeutic molecules
mucosal immunity
safe for consumption
author_facet Laísa M. Tavares
Luís C. L. de Jesus
Tales F. da Silva
Fernanda A. L. Barroso
Viviane L. Batista
Nina D. Coelho-Rocha
Vasco Azevedo
Mariana M. Drumond
Mariana M. Drumond
Pamela Mancha-Agresti
Pamela Mancha-Agresti
author_sort Laísa M. Tavares
title Novel Strategies for Efficient Production and Delivery of Live Biotherapeutics and Biotechnological Uses of Lactococcus lactis: The Lactic Acid Bacterium Model
title_short Novel Strategies for Efficient Production and Delivery of Live Biotherapeutics and Biotechnological Uses of Lactococcus lactis: The Lactic Acid Bacterium Model
title_full Novel Strategies for Efficient Production and Delivery of Live Biotherapeutics and Biotechnological Uses of Lactococcus lactis: The Lactic Acid Bacterium Model
title_fullStr Novel Strategies for Efficient Production and Delivery of Live Biotherapeutics and Biotechnological Uses of Lactococcus lactis: The Lactic Acid Bacterium Model
title_full_unstemmed Novel Strategies for Efficient Production and Delivery of Live Biotherapeutics and Biotechnological Uses of Lactococcus lactis: The Lactic Acid Bacterium Model
title_sort novel strategies for efficient production and delivery of live biotherapeutics and biotechnological uses of lactococcus lactis: the lactic acid bacterium model
publisher Frontiers Media S.A.
series Frontiers in Bioengineering and Biotechnology
issn 2296-4185
publishDate 2020-11-01
description Lactic acid bacteria (LAB) are traditionally used in fermentation and food preservation processes and are recognized as safe for consumption. Recently, they have attracted attention due to their health-promoting properties; many species are already widely used as probiotics for treatment or prevention of various medical conditions, including inflammatory bowel diseases, infections, and autoimmune disorders. Some LAB, especially Lactococcus lactis, have been engineered as live vehicles for delivery of DNA vaccines and for production of therapeutic biomolecules. Here, we summarize work on engineering of LAB, with emphasis on the model LAB, L. lactis. We review the various expression systems for the production of heterologous proteins in Lactococcus spp. and its use as a live delivery system of DNA vaccines and for expression of biotherapeutics using the eukaryotic cell machinery. We have included examples of molecules produced by these expression platforms and their application in clinical disorders. We also present the CRISPR-Cas approach as a novel methodology for the development and optimization of food-grade expression of useful substances, and detail methods to improve DNA delivery by LAB to the gastrointestinal tract. Finally, we discuss perspectives for the development of medical applications of recombinant LABs involving animal model studies and human clinical trials, and we touch on the main safety issues that need to be taken into account so that bioengineered versions of these generally recognized as safe organisms will be considered acceptable for medical use.
topic Lactococcus lactis
genetic engineering
biotherapeutic molecules
mucosal immunity
safe for consumption
url https://www.frontiersin.org/articles/10.3389/fbioe.2020.517166/full
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