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

Applications of synthetic biology in medical and pharmaceutical fields. ​

Literature Information ​

DOI10.1038/s41392-023-01440-5
PMID37169742
JournalSignal transduction and targeted therapy
Impact Factor52.7
JCR QuartileQ1
Publication Year2023
Times Cited35
KeywordsSynthetic Biology, Medical Applications, Pharmaceutical Production, Genetic Circuits, Metabolic Engineering
Literature TypeJournal Article, Review, Research Support, Non-U.S. Gov't
ISSN2059-3635
Pages199
Issue8(1)
AuthorsXu Yan, Xu Liu, Cuihuan Zhao, Guo-Qiang Chen

TL;DR ​

This review highlights the advancements in synthetic biology, which has evolved to create engineered biocircuits and enhance microbial production of pharmaceuticals, as well as develop novel therapeutic strategies for complex medical conditions such as cancer and diabetes. The findings underscore the transformative potential of synthetic biology in addressing unmet medical needs and improving therapeutic efficacy through innovative biological engineering approaches.

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Synthetic Biology · Medical Applications · Pharmaceutical Production · Genetic Circuits · Metabolic Engineering

Abstract ​

Synthetic biology aims to design or assemble existing bioparts or bio-components for useful bioproperties. During the past decades, progresses have been made to build delicate biocircuits, standardized biological building blocks and to develop various genomic/metabolic engineering tools and approaches. Medical and pharmaceutical demands have also pushed the development of synthetic biology, including integration of heterologous pathways into designer cells to efficiently produce medical agents, enhanced yields of natural products in cell growth media to equal or higher than that of the extracts from plants or fungi, constructions of novel genetic circuits for tumor targeting, controllable releases of therapeutic agents in response to specific biomarkers to fight diseases such as diabetes and cancers. Besides, new strategies are developed to treat complex immune diseases, infectious diseases and metabolic disorders that are hard to cure via traditional approaches. In general, synthetic biology brings new capabilities to medical and pharmaceutical researches. This review summarizes the timeline of synthetic biology developments, the past and present of synthetic biology for microbial productions of pharmaceutics, engineered cells equipped with synthetic DNA circuits for diagnosis and therapies, live and auto-assemblied biomaterials for medical treatments, cell-free synthetic biology in medical and pharmaceutical fields, and DNA engineering approaches with potentials for biomedical applications.

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Primary Questions Addressed ​

  1. What are the specific challenges faced in integrating heterologous pathways into designer cells for medical applications?
  2. How do engineered cells with synthetic DNA circuits enhance the diagnosis and treatment of diseases compared to traditional methods?
  3. In what ways can synthetic biology contribute to the development of novel therapies for complex immune diseases?
  4. What advancements have been made in cell-free synthetic biology that could revolutionize pharmaceutical production?
  5. How does the timeline of synthetic biology developments correlate with breakthroughs in the treatment of metabolic disorders?

Key Findings ​

Research Background and Objectives ​

Synthetic biology is a multidisciplinary field focused on designing and constructing new biological parts, devices, and systems, or re-designing existing biological systems for useful purposes. The increasing medical and pharmaceutical demands have accelerated the development of synthetic biology applications, including the production of therapeutic agents, targeted drug delivery, and the treatment of complex diseases.

Main Methods/Materials/Experimental Design ​

The review discusses various synthetic biology approaches in medical and pharmaceutical applications, emphasizing engineered cells, genetic circuits, and biomaterials. The methodologies include:

  1. Engineering Living Cells:

    • Utilization of mammalian, bacterial, and yeast cells as chassis for therapeutic production.
    • Application of CRISPR/Cas9 and other genome editing technologies for precise modifications.

  2. Synthetic Gene Circuits:

    • Construction of circuits that allow cells to respond to environmental signals (e.g., light, chemicals).
    • Integration of feedback mechanisms to control metabolic pathways.

  3. Cell-Free Systems:

    • Use of cell lysates or purified components for protein synthesis and biosensor applications.
    • High-throughput screening for rapid evaluation of therapeutic efficacy.

  4. Nanotechnology:

    • Development of nanocarriers for targeted drug delivery and biosensing.
    • Engineering of nanoparticles for use in conjunction with living cells.
Mermaid diagram

Key Results and Findings ​

  1. Therapeutic Applications:

    • Engineered CAR-T cells have shown promise in treating cancers like acute lymphoblastic leukemia and large B-cell lymphoma.
    • Synthetic biology has enabled the production of complex drugs, including terpenoids and alkaloids, in microbial systems, significantly improving yield and reducing costs.

  2. Innovative Drug Delivery Systems:

    • Development of engineered bacterial systems capable of targeting tumors and delivering therapeutic agents.
    • Cell-free systems provide rapid production of proteins and antibodies, overcoming challenges faced in traditional cell-based systems.

  3. Nanotechnology in Medicine:

    • Nanoparticles have been utilized for controlled drug release and targeted therapies, enhancing treatment efficacy and minimizing side effects.

  4. Bacterial Live Therapeutics:

    • Engineered probiotics have been shown to regulate metabolic disorders and inflammatory diseases effectively.

Main Conclusions/Significance/Innovation ​

The advancements in synthetic biology represent a significant shift in medical and pharmaceutical research, offering innovative solutions for complex health challenges. The ability to engineer living systems and create synthetic circuits provides a framework for developing personalized medicine and targeted therapies. The integration of AI with synthetic biology holds potential for accelerating research and enhancing therapeutic strategies.

Research Limitations and Future Directions ​

Despite the progress, several challenges remain:

  • Safety and Efficacy: Ensuring the safety of engineered organisms in clinical applications is paramount.
  • Regulatory Hurdles: Navigating the regulatory landscape for synthetic biology products can be complex.
  • Scalability: Moving from laboratory-scale successes to industrial-scale applications requires further optimization.

Future research should focus on:

  • Enhancing the robustness and stability of engineered systems.
  • Expanding the range of therapeutic applications.
  • Addressing ethical and social implications associated with synthetic biology.

In conclusion, while synthetic biology has the potential to revolutionize medicine, ongoing research and collaboration across disciplines are essential to realize its full benefits.

References ​

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Literatures Citing This Work ​

  1. Artificial Intelligence Methods for the Construction and Management of Buildings. - Svetlana Ivanova;Aleksandr Kuznetsov;Roman Zverev;Artem Rada - Sensors (Basel, Switzerland) (2023)
  2. Programmable synthetic receptors: the next-generation of cell and gene therapies. - Fei Teng;Tongtong Cui;Li Zhou;Qingqin Gao;Qi Zhou;Wei Li - Signal transduction and targeted therapy (2024)
  3. Investigation of dynamical flexibility of D5SIC-DNAM inside DNA duplex in aqueous solution: a systematic classical MD approach. - Tanay Debnath;G Andrés Cisneros - Physical chemistry chemical physics : PCCP (2024)
  4. The whack-a-mole governance challenge for AI-enabled synthetic biology: literature review and emerging frameworks. - Trond Arne Undheim - Frontiers in bioengineering and biotechnology (2024)
  5. BioCloneBot: A versatile, low-cost, and open-source automated liquid handler. - Ke'Koa Cdh Wells;Nawwaf Kharma;Brandon B Jaunky;Kaiyu Nie;Gabriel Aguiar-Tawil;Daniel Berry - HardwareX (2024)
  6. Cell-Free Synthesis: Expediting Biomanufacturing of Chemical and Biological Molecules. - So-Jeong Lee;Dong-Myung Kim - Molecules (Basel, Switzerland) (2024)
  7. Molecular Engineering of Functional SiRNA Agents. - Neelu Batra;Mei-Juan Tu;Ai-Ming Yu - ACS synthetic biology (2024)
  8. Physiochemically and Genetically Engineered Bacteria: Instructive Design Principles and Diverse Applications. - Xia Lin;Rong Jiao;Haowen Cui;Xuebing Yan;Kun Zhang - Advanced science (Weinheim, Baden-Wurttemberg, Germany) (2024)
  9. Disentangling the Web: An Interdisciplinary Review on the Potential and Feasibility of Spider Silk Bioproduction. - Ghita Guessous;Lauren Blake;Anthony Bui;Yelim Woo;Gabriel Manzanarez - ACS biomaterials science & engineering (2024)
  10. Engineering signalling pathways in mammalian cells. - Anna V Leopold;Vladislav V Verkhusha - Nature biomedical engineering (2024)

... (25 more literatures)

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