Curated Papers > In recent years, high-impact research in "synthetic biology" (IF ≥ 30, last 5 years)

Engineering living therapeutics with synthetic biology.

Literature Information

DOI	10.1038/s41573-021-00285-3
PMID	34616030
Journal	Nature reviews. Drug discovery
Impact Factor	101.8
JCR Quartile	Q1
Publication Year	2021
Times Cited	115
Keywords	Synthetic Biology, Living Therapeutics, Gene Circuits
Literature Type	Journal Article, Review
ISSN	1474-1776
Pages	941-960
Issue	20(12)
Authors	Andres Cubillos-Ruiz, Tingxi Guo, Anna Sokolovska, Paul F Miller, James J Collins, Timothy K Lu, Jose M Lora

TL;DR

This study explores the application of synthetic biology in engineering cells with synthetic gene circuits to create novel therapeutics that can precisely target disease biomarkers, offering advantages over traditional treatments in flexibility, specificity, and predictability. Highlighting significant advancements in engineered cells designed for biological sensing and therapeutic functions, the research underscores the potential of cell-based therapies to revolutionize the treatment of various human diseases.

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Synthetic Biology · Living Therapeutics · Gene Circuits

Abstract

The steadfast advance of the synthetic biology field has enabled scientists to use genetically engineered cells, instead of small molecules or biologics, as the basis for the development of novel therapeutics. Cells endowed with synthetic gene circuits can control the localization, timing and dosage of therapeutic activities in response to specific disease biomarkers and thus represent a powerful new weapon in the fight against disease. Here, we conceptualize how synthetic biology approaches can be applied to programme living cells with therapeutic functions and discuss the advantages that they offer over conventional therapies in terms of flexibility, specificity and predictability, as well as challenges for their development. We present notable advances in the creation of engineered cells that harbour synthetic gene circuits capable of biological sensing and computation of signals derived from intracellular or extracellular biomarkers. We categorize and describe these developments based on the cell scaffold (human or microbial) and the site at which the engineered cell exerts its therapeutic function within its human host. The design of cell-based therapeutics with synthetic biology is a rapidly growing strategy in medicine that holds great promise for the development of effective treatments for a wide variety of human diseases.

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Primary Questions Addressed

1. What specific disease biomarkers are currently being targeted by engineered cells in synthetic biology?
2. How do the therapeutic outcomes of living therapeutics compare to traditional small molecule treatments in clinical settings?
3. What are the ethical considerations and regulatory challenges associated with the use of genetically engineered cells in therapy?
4. In what ways can synthetic biology enhance the specificity and predictability of therapeutic interventions compared to conventional methods?
5. What are the limitations of current synthetic gene circuits in engineered cells, and how might future advancements address these issues?

Key Findings

1. Research Background and Purpose: The field of synthetic biology has made significant strides, allowing researchers to engineer living cells to serve as innovative therapeutics. Traditional treatment methods often rely on small molecules or biologics, which can lack the specificity and adaptability needed for effective disease management. This research aims to explore how synthetic biology can be leveraged to program living cells with therapeutic functions, enhancing their ability to respond to disease biomarkers and offering a new avenue for treatment.

2. Main Methods and Findings: The authors conceptualize the application of synthetic biology in creating engineered cells equipped with synthetic gene circuits. These circuits enable cells to sense biological signals and compute responses based on the presence of specific intracellular or extracellular biomarkers associated with diseases. The research categorizes advancements based on the type of cell utilized (human or microbial) and the therapeutic site of action within the human body. Key findings highlight the development of engineered cells that can control the localization, timing, and dosage of therapeutic actions, significantly enhancing the precision and effectiveness of treatment strategies compared to conventional therapies.

3. Key Conclusions: The research concludes that the design of cell-based therapeutics through synthetic biology represents a transformative approach in medicine. Engineered cells can offer greater flexibility, specificity, and predictability in therapeutic interventions, making them a powerful alternative to traditional treatment modalities. However, the development of these living therapeutics comes with challenges that need to be addressed to ensure their successful implementation in clinical settings.

4. Research Significance and Impact: This study holds substantial significance as it positions synthetic biology as a frontier in therapeutic development, potentially revolutionizing how diseases are treated. By programming living cells to act intelligently in response to disease markers, there is a promise of more effective therapies with reduced side effects. The implications of this research extend beyond treating existing diseases; it also opens pathways for innovative strategies in personalized medicine, where therapies can be tailored to individual patient profiles. The advancements discussed suggest a paradigm shift in therapeutic development, with the potential to improve patient outcomes across a wide variety of health conditions.

References

1. The importance of synthetic chemistry in the pharmaceutical industry. - Kevin R Campos;Paul J Coleman;Juan C Alvarez;Spencer D Dreher;Robert M Garbaccio;Nicholas K Terrett;Richard D Tillyer;Matthew D Truppo;Emma R Parmee - Science (New York, N.Y.) (2019)
2. A brief history of synthetic biology. - D Ewen Cameron;Caleb J Bashor;James J Collins - Nature reviews. Microbiology (2014)
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5. Synthetic biology: integrated gene circuits. - Nagarajan Nandagopal;Michael B Elowitz - Science (New York, N.Y.) (2011)
6. Towards a circuit engineering discipline. - H H McAdams;A Arkin - Current biology : CB (2000)
7. Diversity-based, model-guided construction of synthetic gene networks with predicted functions. - Tom Ellis;Xiao Wang;James J Collins - Nature biotechnology (2009)
8. Programmable cells: interfacing natural and engineered gene networks. - Hideki Kobayashi;Mads Kaern;Michihiro Araki;Kristy Chung;Timothy S Gardner;Charles R Cantor;James J Collins - Proceedings of the National Academy of Sciences of the United States of America (2004)
9. Programming gene and engineered-cell therapies with synthetic biology. - Tasuku Kitada;Breanna DiAndreth;Brian Teague;Ron Weiss - Science (New York, N.Y.) (2018)
10. Designing cell function: assembly of synthetic gene circuits for cell biology applications. - Mingqi Xie;Martin Fussenegger - Nature reviews. Molecular cell biology (2018)

Literatures Citing This Work

1. Emerging Therapeutic Agents for Colorectal Cancer. - Marianna Nalli;Michela Puxeddu;Giuseppe La Regina;Stefano Gianni;Romano Silvestri - Molecules (Basel, Switzerland) (2021)
2. A single layer artificial neural network type architecture with molecular engineered bacteria for reversible and irreversible computing. - Kathakali Sarkar;Deepro Bonnerjee;Rajkamal Srivastava;Sangram Bagh - Chemical science (2021)
3. The Future Potential of Biosensors to Investigate the Gut-Brain Axis. - Jiefei Wang;W Seth Childers - Frontiers in bioengineering and biotechnology (2021)
4. Microbial Biocontainment Systems for Clinical, Agricultural, and Industrial Applications. - Aaron Pantoja Angles;Alexander U Valle-Pérez;Charlotte Hauser;Magdy M Mahfouz - Frontiers in bioengineering and biotechnology (2022)
5. Emerging strategies for engineering Escherichia coli Nissle 1917-based therapeutics. - Jason P Lynch;Lisa Goers;Cammie F Lesser - Trends in pharmacological sciences (2022)
6. Editorial: Synthetic Live Biotherapeutic Products for Diseases. - Ye Chen;Shuyi Zhang - Frontiers in molecular biosciences (2022)
7. CAR-T Cell Performance: How to Improve Their Persistence? - Gina López-Cantillo;Claudia Urueña;Bernardo Armando Camacho;Cesar Ramírez-Segura - Frontiers in immunology (2022)
8. Current Status and Future Directions of Bacteria-Based Immunotherapy. - Quan Tang;Xian Peng;Bo Xu;Xuedong Zhou;Jing Chen;Lei Cheng - Frontiers in immunology (2022)
9. Enhanced protein translocation to mammalian cells by expression of EtgA transglycosylase in a synthetic injector E. coli strain. - Beatriz Álvarez;Víctor Muñoz-Abad;Alejandro Asensio-Calavia;Luis Ángel Fernández - Microbial cell factories (2022)
10. Contemporary exploitation of natural products for arthropod-borne pathogen transmission-blocking interventions. - Jackson M Muema;Joel L Bargul;Meshack A Obonyo;Sospeter N Njeru;Damaris Matoke-Muhia;James M Mutunga - Parasites & vectors (2022)

... (105 more literatures)

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