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文献精选 > 近年高分"合成生物学"研究（IF≥30，近5年）

Engineering living therapeutics with synthetic biology. ​

文献信息 ​

DOI10.1038/s41573-021-00285-3
PMID34616030
期刊Nature reviews. Drug discovery
影响因子101.8
JCR 分区Q1
发表年份2021
被引次数115
关键词合成生物学, 基因电路, 细胞治疗
文献类型Journal Article, Review
ISSN1474-1776
页码941-960
期号20(12)
作者Andres Cubillos-Ruiz, Tingxi Guo, Anna Sokolovska, Paul F Miller, James J Collins, Timothy K Lu, Jose M Lora

一句话小结 ​

合成生物学的进步使得科学家能够利用工程细胞开发针对特定疾病的治疗药物，这些细胞通过合成基因电路根据生物标志物调控治疗活动，展现出比传统疗法更高的灵活性、特异性和可预测性。本文探讨了这一领域的最新进展及其在医学中的应用潜力，强调了合成生物学在应对多种人类疾病中的重要性。

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合成生物学 · 基因电路 · 细胞治疗

摘要 ​

合成生物学领域的稳步发展使科学家能够利用基因工程细胞，而不是小分子或生物制剂，作为开发新型治疗药物的基础。赋予合成基因电路的细胞能够根据特定疾病生物标志物控制治疗活动的定位、时机和剂量，从而成为对抗疾病的一种强大新武器。在这里，我们构思了如何将合成生物学方法应用于编程具有治疗功能的活细胞，并讨论了它们在灵活性、特异性和可预测性方面相较于传统疗法所提供的优势，以及其开发面临的挑战。我们展示了在创建具有生物传感和信号计算能力的合成基因电路的工程细胞方面取得的显著进展。我们根据细胞支架（人类或微生物）以及工程细胞在其人类宿主中发挥治疗功能的位置对这些发展进行了分类和描述。利用合成生物学设计细胞基础的治疗药物是医学中一种迅速发展的策略，具有为多种人类疾病开发有效治疗方案的巨大潜力。

英文摘要 ​

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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主要研究问题 ​

  1. 如何评估合成生物学工程细胞在治疗不同疾病中的有效性和安全性？
  2. 在合成生物学中，哪些新兴技术可以提高工程细胞的治疗特异性和灵活性？
  3. 合成生物学的工程细胞在临床应用中面临哪些主要挑战，如何克服这些挑战？
  4. 未来的合成生物学疗法如何与现有的传统疗法结合，以提高治疗效果？
  5. 不同类型的细胞支架（人类细胞与微生物细胞）在合成生物学治疗中的应用前景如何？

核心洞察 ​

1. 研究背景和目的 ​

随着合成生物学领域的迅速发展，科学家们开始探索用基因工程改造的细胞，取代传统的小分子药物或生物制剂，作为新型治疗方法的基础。传统治疗方法往往存在灵活性不足、特异性差以及治疗效果不可预测等问题。该研究的目的是探讨如何通过合成生物学的方法，设计和编程具备治疗功能的活细胞，从而提供更为精准和有效的疾病治疗手段。

2. 主要方法和发现 ​

研究中，科学家们利用合成基因电路赋予细胞特定的生物功能，使其能够根据特定的疾病生物标志物调控治疗活动的定位、时机和剂量。这些合成基因电路能够对内源性或外源性生物标志物进行生物感应和信号计算。研究团队将这些工程化细胞的进展按细胞支架（人类或微生物）和工程细胞在宿主体内施展治疗功能的部位进行分类和描述，展示了这些细胞在不同疾病背景下的应用潜力。

3. 核心结论 ​

合成生物学方法设计的活细胞治疗策略具有相较于传统疗法的明显优势，包括更高的灵活性、特异性及可预测性。这些工程细胞不仅能针对特定的疾病状态进行精准治疗，还能实时监测和调整其治疗行为，从而提高治疗效果和减小副作用。尽管这些技术展现出广阔的前景，但在开发过程中仍面临诸多挑战，如细胞稳定性、体内持续性和伦理问题等。

4. 研究意义和影响 ​

本研究的意义在于提供了一种全新的视角来看待疾病治疗，即通过编程活细胞实现个性化和精准医疗。这一策略不仅拓宽了治疗的选项，更为解决许多难治疾病提供了可能的解决方案。合成生物学的应用有望推动医学领域的革命性变革，促进新型治疗方法的研发，使之更具针对性和有效性，对改善患者的生活质量和健康水平具有深远的影响。

参考文献 ​

  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)
  3. Construction of a genetic toggle switch in Escherichia coli. - T S Gardner;C R Cantor;J J Collins - Nature (2000)
  4. A synthetic oscillatory network of transcriptional regulators. - M B Elowitz;S Leibler - Nature (2000)
  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)

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  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)

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