Synthetic Biology for Therapeutics: Engineering Cells for Living Drugs

Synthetic biology is enabling scientists to use engineered genetic circuits in the cells as the basis for the development of new living therapeutics and as a powerful new weapon in the fight against diseases, especially cancer. Bacteria-mediated therapy is a promising alternative cancer treatment. The book covers the recent developments of cellular therapies from a synthetic biology perspective including engineered microbial therapies, CAR-T therapies etc. and is an indispensable guide to scientists in both biotechnology and medicine. Synthetic biology applications in programming cells and developing living drugs. Biological devices for cellular targeting. Engineering mammalian and microbial cells for cancer therapies. Cover Half Title Also of interest Synthetic Biology for Therapeutics: Engineering Cells for Living Drugs Copyright Dedication Contents List of contributing authors 1. Programming cells with synthetic biology 1.1 Introduction 1.2 DNA technologies for cell reprogramming 1.2.1 De novo DNA synthesis 1.2.2 Molecular cloning and recombinant vector plasmids 1.2.3 Recombinant DNA transfer into cell hosts 1.2.4 Genome engineering with CRISPR-Cas systems 1.3 Sensing modules 1.3.1 Transcriptional sensing strategies 1.3.2 Translational sensing strategies 1.3.3 Synthetic modular biosensor design 1.3.4 Optimization of sensing dynamics 1.3.5 Engineering sensitivity and specificity 1.4 Signal processing modules 1.4.1 Memory circuits 1.4.2 Quorum sensing (QS) 1.4.3 Logic operations 1.4.3.1 AND gate, OR gate, and NOT gate 1.4.3.2 Proteins for logical operations 1.5 Conclusion References 2. Biological devices for cellular targeting and decision-making 2.1 Biological devices in cellular targeting 2.1.1 Significance of targeting specific cells 2.1.2 Cellular targeting strategies and applications 2.1.2.1 Ligand–receptor interactions 2.1.2.2 Cellular markers and recognition 2.1.2.3 Tissue-specific promoters 2.2 Decision-making in cellular systems 2.2.1 Cellular decision-making and information processing 2.2.1.1 Basis of decision-making 2.2.1.2 Cell fate decision-making applications 2.2.2 Programmable functionalities 2.2.2.1 Advanced bioproduction of therapeutics 2.3 Synthetic biology tools 2.3.1 Usage of electronic circuits as an analogy for decision making 2.3.2 Controllable cellular systems: different stages of translation control 2.3.2.1 Inducible systems 2.3.2.1.1 Light-inducible systems 2.3.2.1.2 Oligonucleotide- and peptide-inducible systems 2.3.2.1.3 Chemically inducible systems 2.3.2.1.4 Heat-inducible systems 2.3.2.1.5 Electric stimulated systems 2.3.2.1.6 Ultrasound stimulated systems 2.4 Conclusion References 3. Engineering mammalian cell for cancer 3.1 Introduction 3.2 Engineering protein secretion 3.2.1 Signal peptides and optimization of signal peptides for enhanced secretion 3.2.2 Cell line development to improve secretion efficiency 3.2.3 Manipulating vesicle transport for improved protein secretion 3.2.4 Genetic engineering (knockdown or knockout strategies) of host cells for enhanced secretion 3.3 Engineering glycosylation 3.3.1 Types of glycosylation 3.3.1.1 N-linked glycosylation 3.3.1.2 O-linked glycosylation 3.3.2 Strategies for engineering glycosylation 3.3.2.1 N-glycosylation engineering 3.3.2.2 O-glycosylation engineering 3.4 Engineering cellular communication 3.4.1 Extracellular vesicles 3.4.2 Manipulating direct cell contact for diagnosis and therapy 3.5 Engineering cellular metabolism 3.6 Conclusion References 4. Engineering microbial cells for cancer 4.1 Introduction 4.1.1 Microbiome–host interactions 4.1.2 Gut microbiome and cancer 4.1.2.1 Role of microbes in cancer development 4.1.2.2 Interactions between microbiome and immune system and TME 4.1.2.3 Impact of microbiome on cancer therapy 4.1.2.4 Bacterial cancer therapy 4.2 Principles of engineering bacterial cancer therapies 4.2.1 Bacterial host selection 4.2.2 Engineering strategies 4.2.2.1 Attenuations and genetic modifications of bacterial strains 4.2.2.2 Sense and response elements 4.2.2.3 Designing genetic circuits for targeted therapeutic delivery systems 4.3 Bacterial cancer therapy in clinical trials and their regulations for safety 4.3.1 Studies in clinical trials 4.3.2 Regulations of safety and efficacy and concluding remarks References 5. New generation cellular engineering for living therapeutics 5.1 Introduction 5.1.1 A paradigm shift 5.1.2 Cellular engineering in therapeutics 5.2 The human microbiome as a therapeutic platform 5.2.1 Microbiome of the human body as potential living therapeutics 5.2.2 Probiotic supplementation as a living therapeutic platform 5.2.3 Cellular programming with synthetic biology for living therapeutics 5.3 Engineered living materials (ELMs) as therapeutics 5.3.1 Engineering biofilm systems as therapeutic ELMs 5.3.1.1 Curli biofilms of E. coli 5.3.1.2 TasA biofilms of B. subtilis 5.3.1.3 L. lactis biofilms 5.3.1.4 Bacterial cellulose 5.3.2 Chemical and biomarker detection with ELMs 5.3.3 Biomineralization as a tool for therapeutic ELMs 5.4 Cross-disciplinary partnership in therapeutic development 5.4.1 The role of bioinformatics and computational biology in living therapeutics 5.5 Challenges and limitations 5.6 Future perspective 5.7 Conclusion References Index Cover back