Applications of synthetic biology in medical and pharmaceutical fields

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.

Fig. 1

Timeline of major milestones in synthetic biology. The timeline begins at 1950s and expands to 2020s. Important events are listed in the right panels

Fig. 2

Development of smart living cells based on synthetic biology strategies. Smart cells can sense various environmental biomarkers, from chemicals to proteins. External signals are transducted into cells to trigger downstream responses. The products are also in the form of chemicals to proteins for customized demands. The sensing-reponsing system is endowing cells with new or enhanced abilities. P represents promoters

Fig. 3

Synthetic biology in the designs of chimeric antigen receptors (CAR). a The AND gate used in artificial CARs. Three typical CARs i.e. Costimulation domain-based second-generation CAR, synNotch receptor-assisted CAR with multiple recognization mechanisms and chimeric costimulation receptor (CCR)-based CAR are exhibited from left to right. b The artificial CARs with inhibitory CAR (iCAR) system. The system can prevent recognizing self-antigens on somatic cells. c The artificial CARs sensing different tumor antigens. Two ScFvs recognizing different targets are tandemly fused, the engineered CAR can be triggered by multiple antigens. The figure is inspired by the paper

Fig. 4

The designs and applications in synthetic material biology. Generally, a genetic circuit is constructed to synthesize biological materials or sense environments. The engineered bacteria are endowed with new characteristics like color change and unique surface properties. The applications for cells with excellular matrices are diverse including magnet field induced therapies, development of novel drug carrier or health monitoring via sophiscated biofabrication processes. This figure is partially inspired by the paper

Fig. 5

Technologies commonly used in synthetic biology. Various synthetic biology methods and tools have been developed to promote the design-build-test-learn cycle of cell factory construction, and these technologies are reforming the medical uses for synthetic biology. Pathway design is the first step, primary results are acquired via the constructed genetic circuits. Some optimizations are needed before next-round of tests, and the characteristics of the system is better understood from preliminary data. The design-build-test-learn cycles are iterative processes to improve robustness and efficacy of synthetic biology systems

Fig. 6

The charasteristics of cell-free synthetic biology. The types, advantages, products, and bottlenecks of cell-free systems are summarized in this figure. Generally, cell-free systems are used to produce pharmaceuticals or served as in vitro sensors. The main advantages are convenient, flexible and high tolerance to cytotoxicity. After solving the problems like high cost and instabilities, the system is promising for actual medical applications

Fig. 7

The present situations, technical bottlenecks and future developments of synthetic biology based gene therapies. Some diagnosis and therapeutical approaches are available via rewiring metabolic and (or) signaling pathways in present synthetic biology. However, some bottlenecks like safety, versatility and efficacy are needing to tackle. Besides, novel designs such as AI-aided synthetic biology and rationally constructed live organisms and proteins are progressing