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Synthetic biology in the clinic: engineering vaccines, diagnostics, and therapeutics.
Literature Information
| DOI | 10.1016/j.cell.2021.01.017 |
|---|---|
| PMID | 33571426 |
| Journal | Cell |
| Impact Factor | 42.5 |
| JCR Quartile | Q1 |
| Publication Year | 2021 |
| Times Cited | 42 |
| Keywords | Synthetic Biology, Vaccine Development, Molecular Diagnostics, Cell-based Therapeutics |
| Literature Type | Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Review |
| ISSN | 0092-8674 |
| Pages | 881-898 |
| Issue | 184(4) |
| Authors | Xiao Tan, Justin H Letendre, James J Collins, Wilson W Wong |
TL;DR
This paper discusses the advancements in synthetic biology, which focuses on engineering new biological functions and has led to promising solutions for significant biomedical challenges, particularly in vaccine development, molecular diagnostics, and cell-based therapeutics. By highlighting technologies that are either clinically approved or in trials, the authors underscore the potential of synthetic biology to revolutionize future biomedical applications.
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Synthetic Biology · Vaccine Development · Molecular Diagnostics · Cell-based Therapeutics
Abstract
Synthetic biology is a design-driven discipline centered on engineering novel biological functions through the discovery, characterization, and repurposing of molecular parts. Several synthetic biological solutions to critical biomedical problems are on the verge of widespread adoption and demonstrate the burgeoning maturation of the field. Here, we highlight applications of synthetic biology in vaccine development, molecular diagnostics, and cell-based therapeutics, emphasizing technologies approved for clinical use or in active clinical trials. We conclude by drawing attention to recent innovations in synthetic biology that are likely to have a significant impact on future applications in biomedicine.
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Primary Questions Addressed
- What are the key challenges in the regulatory approval process for synthetic biology applications in clinical settings?
- How does synthetic biology enhance the efficacy and safety of vaccines compared to traditional vaccine development methods?
- In what ways can synthetic biology contribute to personalized medicine and tailored therapeutic approaches?
- What are the ethical considerations surrounding the use of synthetic biology in human therapeutics and diagnostics?
- How might advancements in synthetic biology influence the future landscape of infectious disease management and prevention?
Key Findings
Research Background and Purpose
Synthetic biology is a rapidly evolving field focused on engineering biological systems for various applications, particularly in medicine. The current global health challenges, including pandemics, highlight the need for innovative solutions in vaccine development, diagnostics, and therapeutics. This review discusses the clinical applications of synthetic biology, emphasizing technologies that have received regulatory approval or are in clinical trials.
Main Methods/Materials/Experimental Design
The review outlines several synthetic biology techniques applied in vaccine development, diagnostics, and therapeutics. Below is a structured overview of the methodologies discussed:
Vaccines: The review discusses genomic codon-deoptimization, DNA, and RNA vaccines, highlighting their design, manufacturing, and clinical trial statuses.
- Genomic Codon-Deoptimization: Uses synonymous mutations to create attenuated viruses for vaccine use.
- DNA Vaccines: Offer stability and prolonged antigen expression but face challenges in immunogenicity.
- RNA Vaccines: Provide rapid design and production capabilities, with notable examples like the Moderna and BioNTech COVID-19 vaccines.
Diagnostics: Focuses on innovative diagnostic tools, particularly:
- Toehold Switch RNA Sensors: Portable, paper-based systems that detect specific nucleic acids.
- CRISPR-based Diagnostics: Techniques like SHERLOCK and DETECTR that utilize CRISPR systems for sensitive nucleic acid detection.
Therapeutics: Covers engineered cell therapies and microbial treatments:
- Cellular Immunotherapy: Includes CAR T-cell therapies with logic circuits to improve specificity and reduce side effects.
- Engineered Microbial Therapies: Rationally designed microbes that restore healthy microbiomes or deliver therapeutic agents.
Key Results and Findings
- Vaccines: Codon-deoptimized vaccines show promise in clinical trials for diseases like influenza and COVID-19, with rapid development timelines.
- Diagnostics: CRISPR-based systems demonstrate high sensitivity and specificity, receiving emergency use authorization for COVID-19 testing.
- Therapeutics: Engineered CAR T-cell therapies exhibit improved efficacy and safety profiles through advanced logic circuits and kill switches.
Main Conclusions/Significance/Innovativeness
The review concludes that synthetic biology has made significant strides in developing innovative medical solutions, particularly in response to urgent health challenges. The ability to rapidly design and deploy vaccines and diagnostics has transformed the biomedical landscape. The integration of synthetic biology into therapeutic strategies holds the potential for personalized medicine and improved patient outcomes.
Research Limitations and Future Directions
- Limitations: The review acknowledges that many synthetic biology applications remain in preclinical stages, and further validation is needed to ensure safety and efficacy in diverse populations.
- Future Directions: Emphasizes the need for continued interdisciplinary collaboration, machine learning integration for design optimization, and the exploration of synthetic biology's potential to create universal vaccines and automated therapeutic systems.
Summary Table
| Category | Key Techniques | Clinical Status |
|---|---|---|
| Vaccines | Codon-deoptimization, DNA, RNA | Various trials, including COVID-19 |
| Diagnostics | Toehold switches, CRISPR | FDA-approved for COVID-19 testing |
| Therapeutics | CAR T-cell therapies, engineered microbes | Ongoing clinical trials |
This structured overview highlights the essential aspects of synthetic biology's contributions to biomedicine, showcasing its potential to revolutionize vaccine development, diagnostics, and therapeutic strategies.
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Literatures Citing This Work
- RNA Engineering for Public Health: Innovations in RNA-Based Diagnostics and Therapeutics. - Walter Thavarajah;Laura M Hertz;David Z Bushhouse;Chloé M Archuleta;Julius B Lucks - Annual review of chemical and biomolecular engineering (2021)
- Synthetic biology as driver for the biologization of materials sciences. - O Burgos-Morales;M Gueye;L Lacombe;C Nowak;R Schmachtenberg;M Hörner;C Jerez-Longres;H Mohsenin;H J Wagner;W Weber - Materials today. Bio (2021)
- Minimally instrumented SHERLOCK (miSHERLOCK) for CRISPR-based point-of-care diagnosis of SARS-CoV-2 and emerging variants. - Helena de Puig;Rose A Lee;Devora Najjar;Xiao Tan;Luis R Soeknsen;Nicolaas M Angenent-Mari;Nina M Donghia;Nicole E Weckman;Audrey Ory;Carlos F Ng;Peter Q Nguyen;Angelo S Mao;Thomas C Ferrante;Geoffrey Lansberry;Hani Sallum;James Niemi;James J Collins - Science advances (2021)
- Integrating United States Biomanufacturing Across Vaccines and Therapeutics. - Krishanu Saha;Krishnendu Roy - NAM perspectives (2021)
- A computational walk to the hidden peaks of protein performance. - Sonja Billerbeck - Synthetic biology (Oxford, England) (2021)
- Therapeutic reversal of Huntington's disease by in vivo self-assembled siRNAs. - Li Zhang;Tengteng Wu;Yangyang Shan;Ge Li;Xue Ni;Xiaorui Chen;Xiuting Hu;Lishan Lin;Yongchao Li;Yalun Guan;Jinfeng Gao;Dingbang Chen;Yu Zhang;Zhong Pei;Xi Chen - Brain : a journal of neurology (2021)
- Programmable Cell-Free Transcriptional Switches for Antibody Detection. - Aitor Patino Diaz;Sara Bracaglia;Simona Ranallo;Tania Patino;Alessandro Porchetta;Francesco Ricci - Journal of the American Chemical Society (2022)
- Development of synthetic biotics as treatment for human diseases. - Aoife M Brennan - Synthetic biology (Oxford, England) (2021)
- An SI-traceable reference material for virus-like particles. - Andrea Briones;Gustavo Martos;Magali Bedu;Tiphaine Choteau;Ralf D Josephs;Robert I Wielgosz;Maxim G Ryadnov - iScience (2022)
- Autonomous push button-controlled rapid insulin release from a piezoelectrically activated subcutaneous cell implant. - Haijie Zhao;Shuai Xue;Marie-Didiée Hussherr;Ana Palma Teixeira;Martin Fussenegger - Science advances (2022)
... (32 more literatures)
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