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Synthetic biology

Synthetic biology

Synthetic biology is a multidisciplinary area of research that seeks to create new biological parts, devices, and systems or redesign systems already found in nature to have new abilities.

Overview

Synthetic biology is the design and engineering of biologically based parts, novel devices, and systems as well as the redesign of existing, natural biological systems. It has the potential to deliver important new applications and improve existing industrial processes, as it is applied to challenges in healthcare, agriculture, manufacturing, and environmental protection and remediation. As a multidisciplinary field, synthetic biology brings together social scientists, biologists, chemists, engineers, mathematicians, and others to identify major challenges in society and collectively find solutions.

Goals of synthetic biology include generating organisms that produce a substance, such as a medicine, agricultural product, or fuel, or gain a new ability, like the ability to sense something in the environment. Other applications include the generation of disease-resistant crops, tissue engineering, and the building of engineered living materials that self-assemble or modulate the performance of a material.

Synthetic biology is not only an applied discipline but also a fundamental discipline. For example, the construction of the minimal bacterial genome, the synthetic yeast project, and parts of the Genome Project-write initiative do not have direct applications but aim to advance our knowledge of genomes. The synthetic biology community has a mindset that is influenced by the phrase by theoretical physicist Richard Feynman, “What I cannot create, I do not understand.” The concept is, when using fundamental principles it should be possible to build up or understand an idea, proof, or concept from the ground up. The idea of understanding by synthesis is a major theme in synthetic biology. Synthetic approaches have not been used in biology to the extent they have been used in other disciplines, such as gaining an understanding of the laws of chemistry through chemical synthesis.

Synthetic biology uses two main working directions for the construction of artificial biological systems with tailored properties: the top-down approach and the bottom-up approach. The top-down approach starts from existing micro-organisms, and the genome is manipulated and reduced based on acquired knowledge to achieve a desired property. The bottom-up approach begins at the molecular level from functional biological devices, like genome, transcriptome, proteome, metabolome, and aims to assemble these biological parts into an artificial cell or synthetic cell. A biodesign platform being developed in synthetic biology uses design-build-test-iterate (or deploy) to create cells or organisms that produce novel materials or to create organisms that perform novel functions.

Similar tools are used in genetic engineering, genome editing, and synthetic biology and a line is sometimes drawn between synthetic biology and the former disciplines by the much larger scale of the manipulations being performed in synthetic biology. Enhancing photosynthesis and the growth of plants is a research area that uses both genetic engineering and synthetic biology. Many biological building blocks are interchangeable between cyanobacteria, algae, and plants, and swapping homologous photosynthetic proteins between species would be genetic engineering. Synthetic biology approaches would involve the exchange of entire multiprotein complexes between distantly related species. Synthetic biology involves building using standardized genetic parts and synthetic biological circuit design.

Some governments have expressed concerns that synthetic biology could increase the number of agents of concern, such as chemical and biological threats, and require the development of detection, identification, and monitoring systems as countermeasures.

History

Biophysicist Stéphane Leduc coined the term synthetic biology and laid out the philosophical and experimental foundations in 1912. Leduc argued that no boundary separates life from physical phenomena, illustrating this by growing chemical gardens of inorganic crystals that resemble living systems. The theoretical basis of contemporary synthetic biology is largely attributed to Waclaw Szybalski’s statements in 1974 related to the invention of recombinant DNA technology.

Up to now we are working on the descriptive phase of molecular biology. … But the real challenge will start when we enter the synthetic biology phase of research in our field. We will then devise new control elements and add these new modules to the existing genomes or build up wholly new genomes. This would be a field with unlimited expansion potential and hardly any limitations to building ‘new better control circuits’ and … finally other ‘synthetic’ organisms …

Rather than a biophysical discipline, contemporary synthetic biology is largely an engineering discipline that emphasizes principles such as standardization, modularity, digital logic, and mathematically predictable behavior. Synthetic biology as an engineering discipline began being discussed around 2005-2006. A possible hierarchy for synthetic biology inspired by computer engineering was described by researchers at Princeton University. DNA, RNA, proteins, and metabolites are analogous to the physical layer of transistors, capacitors, and resistors. Biochemical reactions that regulate the flow of information and manipulate physical processes are analogous to the device layer with logic gates. It is envisioned that synthetic biologists would assemble biological devices into pathways that function like integrated circuits.

Civil engineer Drew Endy and fellow researchers at MIT are recognized as major contributors to synthetic biology and brought forth the BioBricks Foundation dedicated to developing the approach of using the engineering mindset of standardized interchangeable biological parts. Endy and his colleagues also laid the groundwork for the international Genetically Engineered Machines Competition (iGEM), which began as an MIT summer course in 2003. Jay Keasling at University of California, Berkeley contributed to the framing of synthetic biology as a new engineering discipline by engineering yeast to produce artemisinin, used in malaria drugs in 2006. Another contributor to the synthetic biology field is Craig Venter with his work deconstructing micro-organisms to find the minimal amount of genetic material needed for a living cell and building a fully synthetic genome.

Fields that overlap with synthetic biology
Theoretical biology and artificial life
Engineered living materials (ELMs)

Engineered living materials (ELMs) are engineered materials made of living cells able to form or self-assemble material or modulate the functional performance of a material. The foundations of ELMs come from synthetic biology and materials engineering.

Manipulating biology to produce advanced materials has the potential to produce systems possessing living organism characteristics, such as autonomy, adaptability, and self-healing. Such systems could be engineered to produce bulk materials with designed physicochemical or mechanical properties.

Research toward producing engineered living material includes engineered bacterial systems, living composite materials incorporating inorganic components, engineering cells and biofilms as living material, and large-scale living material fabrication and manufacturing methods.

There are two approaches to developing engineering living materials:

  • Bottom-up approach—using programmed cells as bionanomaterials factories for production. This approach incorporates considerable science from synthetic biology and molecular self-assembly.
  • Top-down approach—focusing on synthetic materials research to composite engineered living materials in which inorganic components make up a large part of the material.
Synthetic circuit design

Synthetic circuit design is based on knowledge about genetic circuits used by cells, whereby genes and the proteins they encode interact with each other, respond to internal and environmental cues, and switch on and off cellular processes like gene expression and cell division. Synthetic circuit design uses a bottom-up approach to put together well-characterized genes and proteins to produce synthetic gene circuits that perform desired functions.

The first genetic circuits engineered to carry out designed functions—the genetic toggle switch and the repressilator—were published in 2000. Cells that harbored the genetic toggle switch circuit could toggle between two stable expression states in response to external signals. With the repressilator, activation of an oscillatory circuit resulted in the ordered, periodic oscillation or repressor protein expression. These studies combined quantitative design, physical construction, experimental measurement, and hypothesis-driven debugging to construct synthetic circuits, which became a characteristic feature of constructing synthetic circuits.

Circuits that rely on genes to be transcribed or translated into proteins have a lag time of hours or days between input and output due to the time it takes for these biochemical processes to occur in the cell. Circuits that use protein-protein interactions can be turned on within seconds. Proteins that control cellular processes act like switches with two stable states. A protein can switch between two stable states by a reversible protein modification called phosphorylation, which can be induced by the interaction between two proteins. A toggle switch triggered by sorbitol, a sugar alcohol found in fruits, was designed as a network of fourteen proteins expressed in yeast host cells. When the yeast cell detects sorbitol, it stores the memory of the exposure as a fluorescent protein that moves into the nucleus.

Examples of synthetic biological circuits

  • Asymmetric plasmid partitioning is a synthetic genetic circuit that controls asymmetric cell division in Escherichia coli.
  • Distributed Multicellular Computation is used to divide labor between different cell strains when logic gates are too complex to be implemented by single cells. Boolean logic gates are engineered using transcriptional regulators, RNA molecules, or site-specific recombinases.
  • Recombinase logic devices make use of recombinase enzymes that invert or excise DNA at specific DNA sequences.
Transcriptional control

Circuits based on transcriptional control share a common design consisting of an actuator that controls positive or negative regulation of transcription. This part is connected with a DNA-binding part that recognizes the regulatory DNA sequence called a promoter. These programmable transcription factors are based on natural transcription factors that bind promoters to control gene expression.

  • Zinc-finger (ZF)-containing factors
  • Transcription activator-like effectors
  • Clustered regularly interspaced short palindromic repeats (CRISPR)-based regulators
RNA devices

RNA devices are engineered RNA sequences that combine sensor and actuator components to encode higher-order functions. For example, the binding of a ligand to an RNA sensor alters the activity. RNA sensors use RNA aptamers, short RNA sequences that can detect biological inputs such as nucleic acids, proteins, small molecules, and RNA-lipid interactions. One application of an RNA device is to distinguish between undifferentiated human induced pluripotent stem cells and differentiated cells.

Ribozymes or catalytic RNA are RNA enzymes that catalyze chemical reactions, such as in the ribosome where ribozymes join amino acids together to form protein chains. Effector-responsive ribozymes are engineered by the addition of ligand-binding RNA aptamer sequences that control the activity of the RNA catalyst.

Optogenetic circuits

The optogenetics field has adapted the use of light-responsive proteins to control a variety of cellular functions that can be further engineered or built into biological systems through synthetic biology. Optogenetics uses light as a trigger to cause a photosensitive protein to respond by switching on or off a molecular event that can be measured or detected. Photosensitive proteins used in this way are called optogenetic actuators.

Standardization
Facilitating access to DNA sequences
Whole genome engineering

The generation of customized cells with fully synthetic genomes is another area of synthetic biology. Genome Project-write (GP-write) is an open international research project that plans to reduce the costs of engineering and testing large genomes in cell lines. Through synthesizing whole genomes, GP-write aims to better understand the human genome and other genomes. Related projects include the minimal bacterial genome and Synthetic Yeast 2.0.

Artificial genetic systems

XNAs are synthetic molecules that are artificial genetic systems that can store and pass on genetic information similar to DNA and evolve through natural selection.

Artificial enzymes

Artificial enzymes, capable of triggering chemical reactions like naturally-occurring enzymes, have been developed using molecules that do not occur in nature. The artificial enzymes called XNAzymes were generated using XNAs as building blocks. XNAs are similar to RNA, and like RNA molecules can function as enzymes and catalyze chemical reactions. Three XNAzymes were designed to self-assemble into a nanostructure that targets and cuts at specific RNA sequences, including SARS-CoV-2 virus to inhibit viral infection.

Artificial RNA and artificial enzyme research strive to answer questions about alternative chemistries to ours that could make life possible, potentially on other planets. For medical therapeutic applications, artificial enzymes have the potential to be more stable in the body because they are not degraded as easily.

Technology and tools

Synthetic biology involves designing, engineering, and building biological systems using standardized biological parts. Standardized biological parts include DNA segments that code for proteins and DNA elements that regulate transcription. There are common molecular biology tools and techniques for identifying, isolating, storing, manipulating, and synthesizing these biological parts.

Expand
DNA synthesis or gene synthesis

DNA synthesis is the linking together of nucleotide bases such as the four naturally occurring ones—Adenine, Thymine, Cytosine, and Guanine—to form a DNA molecule. During DNA synthesis, non-natural nucleotide bases may also be incorporated into DNA. The ability to produce large amounts of synthetic DNA on demand is a rate-limiting step in synthetic biology.

Phosphoramidite synthesis

The core technologies for DNA synthesis are based on the chemical method established in the 1980s called phosphoramidite synthesis. Phosphoramidite synthesis proceeds by multiple rounds of stepwise assembly. Each base added to the growing DNA strand has a chemical group that blocks more nucleotide bases from being added and needs to be removed before adding more nucleotides. Over about 120 bases, product yield is about 50%. Larger-scale assemblies must be constructed from smaller strands. The accuracy of phosphoramidite synthesis is good for short DNA lengths of around 200-300 nucleotides but longer DNA sequences require more time to produce error-free DNA. Methods that use enzymes have the potential to generate longer sequences.

Enzymatic synthesis

Enzymatic DNA synthesis uses biological enzymes rather than chemical agents to build DNA. As of 2022, most enzymatic DNA synthesis used terminal deoxynucleotidyl transferase (TdT). TdT does not require a template to incorporate nucleotides. The normal role of TdT in cells is to introduce extra random nucleotides to single-stranded DNA during V(D)J recombination, the process of chromosome breakage, rearrangement, and rejoining, which occurs to generate antibodies and T cell receptors. TdT produces randomization of genetic material that is crucial for the evolution and adaptation of the vertebrate immune system by increasing antigen receptor diversity.

On-chip assembly

Multiple parallel micro-reactions on silicon chips are the methods of next-generation DNA synthesisers and are compatible with both chemical and enzymatic synthesis. A generation of desktop DNA synthesisers are in development that would be based on precision thermal control chips with thousand of pixels or virtual wells that act as individual DNA synthesis sites with continuously flowing liquid. DNA strands are built base-by-base and released from the surface for on-chip assembly. Error correction occurs through thermal purification, in which mismatches between partially assembled DNA strands are detected and removed at a specific temperature.

The following are companies that specialize in DNA synthesis:

DNA sequencing

DNA sequencing is the determination of which nucleotide bases are present and in which precise order they occur within a segment of DNA.

DNA sequencing companies

Gene editing techniques

Gene editing techniques are used to alter specific DNA sequences in the genome or RNA molecules, which are transcripts or copies of the DNA sequence that will be translated into the amino acid sequence of the protein.

Bioinformatics and modeling

Bioinformatics is the use of computational techniques to organize and search biological data as well as model biological systems and solve biological problems.

Bioinformatics companies

Transfection of nucleic acids

Transfection is a procedure used to introduce nucleic acids which may be DNA, RNA, or oligonucleotides into eukaryotic cells.

DNA transfer into prokaryotic cells
  • DNA ENhanced TRAnsfer Platform (DNA ENTRAP) is a microfluidic device that works with the cell-to-cell DNA transfer tool XPORT
Genome/protein engineering tools
Lab equipment workflow solutions
Directed evolution

Directed evolution methods mimic natural selection, but the process is sped up in the laboratory. The system is a method of engineering proteins with desired features because it is set up so certain protein structures or functions have a selective advantage. One form of this method is phage-assisted continuous evolution (PACE).

Phage engineering

Bacteriophages (phages) are viruses that selectively infect specific bacterial strains. Phage components are a rich source of parts to be used in synthetic biology for building genetic circuits. Phages are engineered for use as phage therapies as antimicrobial agents and also for the delivery of drugs and vaccines. Phages can also be engineered to assemble new materials.

Mapping projects

Since synthetic biology aims to redesign or build biological entities using biological parts, mapping how those parts fit together in natural living systems can serve as a guide for how to put parts together to attain a desired function. Mapping and reading genomes has led to writing synthetic genomes that function in bacteria. Systems biology is involved in creating maps of biological interactions involving cells, genes, proteins, and metabolic pathways in healthy and diseased living systems, which can serve as a reference point for synthetic biology. At a meta-level, mapping how different areas of synthetic biology and biological engineering are developing and could evolve in the future can help to identify promising areas for research.

Biological atlases and maps
Omics

Omics technologies are high-throughput biochemical assays that measure the same type of molecule comprehensively and simultaneously in the same biological sample. For example, the molecule profiled may be DNA (genomics), RNA transcripts (transcriptomics), or proteins (proteomics). Multi-omics datasets are combinations of multiple assays from the same sample set. In biomanufacturing, omics datasets are analyzed by machine learning platforms to guide the optimization of biosynthetic pathways.

  • Proteomics
  • Metabolomics
  • Epigenomics
  • Genomics
  • Transcriptomics
  • Microbiome
Companies producing materials for omics
  • BiomeX is a supplier of products and services, such as disease state patient samples, needed to develop, validate, register, and produce diagnostic products.
Blockchain and biology
Blockchain to model biochemical circuits

The recordkeeping capabilities of blockchain could be applied to synthetic circuits. The implementation of logic-based smart contracts was proposed as a computational approach to modeling biochemical circuits. Synthetic biology circuits are usually assayed by detecting fluorescent reporters. Fluorescent reporter proteins are subject to degradation, and it is difficult to encode advanced outputs such as oscillation with multiple repressors using these reporter systems. A global blockchain-based reporter could be used to eliminate the need for individual reporters to validate individual logic gates. For example, the proposed blockchain could be designed as a ledger of the state of a particular cell.

Tracking and security of biological data

The ability of blockchain to facilitate transparency, control, and sharing of information while keeping data secure is being applied to biotechnology with companies like Nebula Genomics aiming for homomorphic encryption of people's genomic data. Blockchain technology in data storage and online platforms can improve sharing and access to information and also provide quicker ways for tracking and managing various steps in drug development.

Synthetic biology is applied in the development of immunotherapies such as CAR-T cell therapy. Blockchain can provide ways to store, maintain, track, and secure information about cells derived from a donor patient like editing performed, storage conditions, and transport from donor to recipient. The information must be accessible to patients, physicians, laboratory scientists, logistics companies, supply chains, and infusion centers.

  • Genexi (blockchain and cryptocurrency marketplace)
  • Orvium (scientific publishing)
Synthetic biology applications
Biofuel

Synthetic biology approaches are used to modify microbes for better production of biofuels, such as cellulosic biofuel.

Synthetic biology improves existing methods for biofuel production from plants and allows for the creation of new "cell factories" that can generate energy from both traditional and non-traditional forms of feedstock. This entails:

  • the generation of industrial enzymes using biosynthetic pathways that improve the yield or quality of biofuel production and
  • the generation of industrial microbes from host organisms to produce strain improvement that is innately capable of generating energy or strain development via importing genes to the host organism such that they can utilize unique feedstocks to generate energy.

The following are advantages of synthetic biology production methods for biofuels:

  • Higher yield, titer, and quality
  • The production of new novel biofuels that are less toxic, more accessible, easier to produce, and have superior properties
  • Reduced cost of the feedstock used, increasing access to renewable and affordable sources of feedstock and streamlining and optimizing production processes
  • Environmentally-friendly processes utilizing natural or waste feedstocks.

The following are examples of biofuels generated using synthetic biology:

  • Biodiesel produced using an industrial phospholipase from Pichia pastoris grown on plant oil feedstocks
  • Biodiesel from renewable farnesene produced from engineered yeast cultured or sugarcane
  • Ethanol from engineered thermophilic microorganisms

Biofuel companies

Cellular agriculture

Synthetic biology is applied to cellular agriculture to genetically engineer cell cultures to provide new or enhanced capabilities to produce agricultural products that are otherwise obtained from animal and plant farming.

Cellular agriculture allows for the production of animal products from cells in a lab rather than raising animals. As a result, it has the potential to:

  • reduce the environmental impact of current agricultural practices;
  • transform how society sources a range of agricultural products from food to more potent plant growth treatments, as well as pesticides and fertilizers that can respond to environmental and organismal conditions (biosensors);
  • produce more food of greater quality and safety; and
  • create entirely new kinds of food with improved properties, such as medicinal value and longer shelf life.

A significant focus of cellular agriculture is cultured meat grown in the lab, with the majority of research working toward the production of common meats such as beef, pork, chicken, fish, and seafood. Other examples of synthetic biology products being developed include synthetic coffee, microbial food cultures for solar energy-based protein powder, and synthetic starch through cell-free artificial synthesis.

Synthetic biology processes utilized within cellular agriculture include the following:

  • Engineering biosynthetic pathways and enzymes to enhance the efficiency of current processes, improve the nutritional value of food, and generate novel food products.
  • Generating specific food types/ingredients or beneficial agricultural metabolites through strain improvement of organisms or strain development through importing useful genes.

There are a variety of examples of synthetic biology contributions through cellular agriculture:

  • Biosynthetic pathways comprised of genes from evolutionary lower organisms that have led to the de novo synthesis of unsaturated healthy fatty acids in an animal
  • The stevia sweetener initially derived from plants is now produced on commercial scales using engineered microorganisms
  • The use of CRISPR technology to produce crops that are beginning to show resistance to fungal diseases
  • Newly engineered microbes which can improve the vitamin content of fermented food such as yogurt and cheese
  • Hypoallergenic peanuts developed using CRISPR technology
  • Chlorella microalgae that can successfully generate butter and oil for both the food and chemical industry

Cellular agriculture companies

Biosensors

In medicine, synthetic molecular and cellular biosensors hold potential in diagnostics and theranostics, whereby gene circuits could act like an intracellular molecular prosthesis, monitoring disease-associated biomarkers and adjusting therapeutic response accordingly.Biosensors can also be used for targeted delivery of therapeutics.

DNA nanorobots—described in Nature Biotechnology in 2018—were constructed using DNA. A DNA aptamer binds nucleolin, a protein expressed in tumor-associated endothelial cells, and binding causes a molecular trigger to open the DNA nanorobot and release the payload at the tumor site.

  • RNA-based biosensing
  • Phage-based diagnostics
  • Paper-based synthetic gene networks
  • Bacterial biosensors
  • Mammalian cell biosensors

Outside of diagnostics, biosensors also have applications in agriculture, environmental protection, food production, and conservation:

  • Whole-cell biosensors are capable of detecting and measuring environmental pollutants, infectious agents, disease, and drug biomarkers. Examples include engineered E.coli containing an arsenic-sensing gene circuit along with an oscillating circuit that generates a fluorescent signal when the heavy metal is present.
  • Enriching soil and feedstock with biosensors to help detect pathogens or contaminants, confers resistance to disease agents, and enhances the quality of animal or plant food products.
  • MiProbes develops biosensors for diagnostics and detection of food contamination.

Biosensor companies

Tissue engineering and regenerative medicine

Synthetic biology approaches are applied to finding ways to control the process of regeneration in the body or the growth of tissue in the lab prior to transplantation into people. Therapeutic benefits could be added to tissues through synthetic biology approaches. Tissues could be engineered to have disease-sensing functionalities. Researchers at University of Toronto aim to improve the ability of future lab-cultured tissues to tolerate low oxygen because these tissues will need to survive a temporary period of low oxygen until it becomes fully integrated with the vasculature of the recipient. Biomaterials used in tissue regeneration can promote specific immune cell interactions and/or signal to other cell types that aid in the regeneration process.

Self-organizing structures

Synthetic biology is applied to tissue engineering and morphogenetic engineering to make genetic manipulations that control the self-organization programs used by multicellular organisms during development and regeneration for the purpose of generating self-assembling structures. A method for the construction of self-assembling structures would use the following sequence: 1) form a pattern, 2) change gene expression, and 3) trigger morphogenesis. Researchers from University of Edinburgh described their construction of a net-like structure by two cell types that formed a pattern, resulting in differential gene expression between the two cell types. The holes in the “net” were formed when a morphogenic effector was used to drive cell death in one cell type.

Bioprinting

3D bioprinting technologies are applied to build vascularized 3D tissues for regenerative medicine and drug testing.

Tissue engineering companies

Biological pest control with genetically engineered organisms

Synthetic speciation is an approach that has been used to generate new species of fruit flies, which are common model organisms in research labs. The approach could be applied to pest control in agriculture or against insect-borne illness. CRISPR-Cas9 tools were used to mutate the DNA of fruit flies to create species that are genetically distinct enough that they cannot interbreed and create offspring.

Gene drive is another approach that uses CRISPR-Cas9 technology to increase the chance that a desired gene is passed on to offspring from the normal 50% to almost 100%. When an animal carrying gene drive mates with one that does not, their offspring get one copy of the gene drive version and one natural version of a gene, but in the fertilized egg, the CRISPR system directs the natural version of the gene to be cut out and the cell repair machinery fixes the missing DNA by replacing it with a copy of the gene drive version of the gene. This results in two copies of the gene drive. Gene drive is applied to the generation of mosquitos that can eradicate a species of mosquito that carries malaria.

  • Oxitec is developing genetically engineering insects as "living insecticides"
Aquaculture

Aquaculture refers to the breeding, rearing, and harvesting of all forms of organisms that inhabit water environments. Aquaculture produces over half of the fish products we eat. Advantages of aquaculture include restoring habitats and boosting wild stocks of both freshwater and seawater species.

There are a variety of synthetic biology applications in aquaculture:

  • Engineering algae that can produce vaccines and therapeutics against bacterial infection in fish populations
  • Replacing wild-caught fish used as feed in aquaculture with engineered algae and microbes to produce a more sustainable aquaculture system
  • Improving aquaculture stock (disease resistance, feed efficiency, growth rate, etc.) using small-scale genome engineering combined with selective breeding

Aquaculture companies

Bioplastic

Synthetic biology can be utilized to generate cells that innately produce bioplastic or engineer organisms to produce bioplastic. Some microbes naturally produce polymers that can be used to make plastics. Polyhydroxyalkanoates (PHAs) used in food packaging and other disposable items are made from polymers produced by microorganisms. With strain and fermentation optimization, companies are able to produce PHAs from bacteria at industrial scales. Also using metabolic and protein engineering, metabolic pathways can be used to produce plastics (e.g. PLA). Bluepha is developing the biodegradable polymer, PHA, generated by fermentation using seawater, and carbon-containing industrial and domestic waste products. Researchers at Yield10 Bioscience produce Camelina seed with high levels of PHA bioplastic and are also working to develop Camelina for the production of oil for renewable diesel and as a fish oil supplement for aquaculture feed.

Bioplastic companies

Biological control systems

Biological control systems is the application of control theory and practice to biological systems. A control engineering perspective on function, organization and coordination are applied to the coordination of multi-scale biological control systems that enable living organisms or cells to carry out functions such as maintaining homeostasis in the face of external and internal influences. From this engineering perspective, diseases arise when one or more biological control systems malfunctions. The tasks to be performed to fix the malfunction in biological control system thinking are as follows: 1) analysis of biological systems, 2) identification of the root cause of pathology, and 3) rational design and implementation of interventions.

Biopharma and health

Synthetic biology approaches are used for designing screening systems for drug discovery, for the design of drugs and for the biomanufacturing of therapeutics and health-related products.

Aging and senescence

Senescence is a state of permanent growth arrest that cells can enter when they are damaged or stressed where they lose the ability to divide but do not undergo cell death. Cellular senescence is both an anticancer mechanism and a contributor to the loss of tissue and organ function over time in aging and age-related disease.

Autoimmune diseases
Cancer
  • Circle Pharma
  • OncoSenX
  • Synthorx
  • Autolus is focused on programmed T-cell therapies for the treatment of cancer
  • Humane Genomics is using synthetic virus engineering for personalized cancer treatments
  • Poseida Therapeutics autologous and allogenic CAR-T product candidates, initially focused on the treatment of hematological malignancies and other solid tumors
  • Prokarium developing vaccination and cancer immunotherapy solutions
  • Cell Design Labs developing a platform for custom cell engineering called synNotch, to be used for cell-based therapies to treat cancer, autoimmune and degenerative disorders
Immunotherapy
  • Senti Biosciences
  • Obsidian Therapeutics is developing cell and gene therapies with pharmacologic operating systems in which a small molecule drug controls the activity of a synthetic biological cassette (focus CAR-T)
Vaccines and infectious disease treatments
Live biotherapeutics
  • AO Biome developed strains of Ammonia Oxidizing Bacteria (AOB) to administer live-in treatments that address inflammatory conditions
  • Mother Dirt is a consumer division of AOBiome that sells personal hygiene products
  • Azitra uses a strain of bacteria from the skin microbiome, S. epidermidis, to modify the skin microbiome and deliver therapeutic protein to the target
  • CHAIN Biotech built a live biotherapeutic platform based on Clostridia to deliver bioactive molecules to treat diseases associated with the human gut microbiome
  • Evolve Biosystems develops microbiome-based products engineered to restore and maintain the gut microbiome
  • Synlogic develops therapeutic probiotics that alter the human gut microbiome to treat diseases
  • Siolta Therapeutics develops microbiome analyses to test microbial-based therapeutics for the treatment and prevention of inflammatory diseases
  • ViThera Pharmaceuticals uses genetically engineered probiotic bacteria as vectors for the delivery of therapeutic proteins for the treatment of inflammatory bowel disease
  • Zbiotics is creating genetically engineered probiotics for consumers such as a bioengineered hangover drink
Drug discovery
  • A-Alpha Bio developed yeast-based screening of protein-protein interactions for drug development
  • Amprologix is developing antibiotics to treat drug-resistant bacterial infections
  • Deep Genomics uses AI to find drugs for genetic disorders
  • Distributed Bio is developing antibody discovery, engineering, informatics tools, and services for the life sciences research and drug discovery
  • LifeMine Therapeutics uses genomics and AI approaches to search for genetically-encoded small molecules in eukaryotic microbes for the discovery of drugs to treat chronic diseases
  • Tierra Biosciences is a drug discovery company using cell-free systems
  • Juno Bio uses machine learning and bioinformatics to analyze microbiomes for the purpose of manipulating them
  • SyntheX uses a proprietary drug design approach and in-vivo screening platform, ToRPPIDO, to identify compounds that disrupt protein-protein interactions
Genetic disease
  • Editas Medicine is using CRISPR technology to treat patients with genetically defined diseases
  • Intellia Therapeutics develops biopharmaceuticals using CRISPR-Cas9 gene editing technology
  • Wave Life Sciences uses a synthetic chemistry platform to design and develop nucleic acid therapeutics that precisely target the underlying cause of rare genetic diseases
Xenotransplantation
  • Egenesis uses gene editing tech for xenotransplantation procedures in the medical industry
Microbiome therapeutics (non live cell)
  • Eligo Bioscience uses proprietary methods in synthetic biology and protein and genome engineering to produce Eligobiotics, delivered CRIPSR-Cas systems, that cut up and destroy the DNA of the target bacteria, and are able to intervene with the microbiome as diagnostics, antimicrobials, and modulators of host-microbiome interactions
Biomanufacturing

Biomanufacturing refers to industrial production that uses biological organisms or parts of biological organisms in an unnatural way to produce a product.

Synthetic biology provides new genomes, biological pathways, or organisms for use in biomanufacturing and allows for the redesign of existing genes, cells, or organisms. These have wide utility in biomanufacturing for commerce and medicine. Synthetic biology allows for the manufacture of new novel products as well as new approaches to existing sectors (gene therapy in healthcare for example). Ginko Bioworks and Lumen bioscience are engineering microorganisms for the manufacturing of food ingredients, therapeutic products, and other materials. Deinove genetically engineers bacteria for the biomanufacturing of antibiotics, bio-based ingredients for cosmetics and nutrition as well as organic acids, ethanol, and biofuels.

Agricultural products

The following are examples of companies using synthetic biology approaches to produce agricultural products:

Pheromone biotechnology

Pheromones are produced as alternatives to pesticides, using synthetic biology approaches to production.

Food industry
Chemicals production
Medical products and dietary supplements
  • Ginko Bioworks
  • Lumen Bioscience
  • Hyasynth Bio engineers microbes for the manufacturing of pharmaceuticals and other products, specifically cannabinoids, including THC
  • Renew BioPharma produces cannabinoids and derivatives using microalgae for the development of therapeutics for neurodegenerative diseases, traumatic brain injuries (TBI), and pain management
  • Teewinot Life Science focuses on the biosynthetic production of pure pharmaceutical-grade cannabinoids from yeast and other microorganisms
  • Biosyntia aims to replace chemical-based vitamin production with sustainable and fermentation-based processes
Carbon capture and conversion

Synthetic biology microorganisms have the potential to convert carbon into biofuels and commodity chemicals. The processes are not currently economically viable but the use of microbial organisms as cell factories that optimize carbon conservation during their metabolic processes is a topic of significant research.

Biomanufacturing companies

Agricultural crop improvement

Plant synthetic biology approaches are applied to engineering metabolic pathways that increase yield and/or make plants resistant to drought or pests. Researchers at Stanford University designed synthetic genetic circuits that modify root structures of plants to make them more efficient at gathering nutrients and water and more resilient to climate challenges.

Engineering of plant-associated microbiomes

The phytomicrobiome is the term for the microorganisms that colonize plants. Phytomicrobiome engineering, or plant microbiome engineering, is an area of synthetic biology. Plant-associated microbes have plant growth-promoting traits. Plant growth-promoting microbes have been isolated which are used as biofertilizers, biostimulants and biocontrol agents.

Plant microbiome engineering can take a bottom-up approach whereby specific microbes are isolated, engineered, and reintroduced to the plant as synthetic microbial communities. The top-down approach involves synthetic ecology and uses horizontal gene transfer to a wide range of hosts in situ, followed by phenotyping the microbiome. For example, mobile genetic elements can be transferred and integrated into a subpopulation of microbiomes to study plant growth-promoting traits in a holistic manner.

Microbial genome engineering tools
  • Phage integrase system
  • ICE system
  • CRAGE system
  • Metabolomics alteration of gut microbiome in situ conjugation (MAGIC) (was first used in mouse gut)
Companies working on phytomicrobiome engineering
  • Synlogic
  • Pivot Bio
  • JOYN Bio
  • NOVOME Biotechnologies
  • 64-X
Biomaterials

Biomaterials are materials that interact with biological systems. They can be natural or synthetic and are usually made of multiple components. They are often used for medical applications such as augmenting or replacing natural functions. Synthetic biology use in biomaterials includes generating synthetically engineered cells that can produce new biomaterials or function as the living component of a new biomaterial.

Biomining

Biomining is the process of using microorganisms to extract metals from ore or mine waste. It also has the potential used to clean up sites polluted by metals.

Synthetic biology research is looking at producing microorganism strains that can be used for the detection, adsorption/chelation, absorption, and bioconversion of metals from their environment.

Biomining companies

Bioprinting

3D bioprinting has potential to use cells and gels for fabrication of functional tissue that could be used for regenerative medicine, pharmaceutical preclinical drug screening and animal-free meat.

Space exploration

A combined approach where microorganisms are engineered to produce biomaterials and those biomaterials are fed into a bioprinter to builds structural materials, food or medicine, has been envisioned to sustain future space missions such as to mars. In this scenario, instructions could be sent digitally to a space crew that allow them to modify the genetics of bacteria to synthesize the needed raw materials that the 3D printer needs to make the items.

Bioprinting companies

Biosafety, biosecurity, and cyberbiosecurity

Genetic engineering of living organisms increases potential bio-risks. Biosecurity is one of the three bio-risks, which are biosafety, biosecurity, and cyberbiosecurity. Biosecurity is the use of proactive measures to avoid intentional biohazards such as theft and misuse of biotechnology and microbiologically hazardous materials. Biosecurity aims to reduce the risks associated with the misuse of synthetic biology which could harm humans, animals, plants, and the environment.

Biosafety is a term that came from the field of microbiology as an abbreviation of safety in biological containment. Biosafety emerged from transgenic biotechnology as an acronym for “safety in biotechnology” and referred to safety associated with genetically modified organisms in the environment. Biosafety can also refer to safety with respect to biological research and the prevention of unintentional biotechnological and microbial biohazards. Vaccination management, exotic species, and access to safe and adequate food supply chains are part of biosafety issues.

Cyberbiosecurity is a hybridized discipline that includes cybersecurity, cyber-physical security and biosecurity applied to biological and biomedical-based systems. Cyberbiosecurity can be thought of as any unforeseeable adverse consequence involving a cyber-physical interface.

Biosafety Organizations

Biosecurity companies

Conferences
Organizations and projects
Start-up incubators and accelerators
Nonprofits
Research labs
Federal organizations
Software tools
Venture capital

Timeline

January 2000
The first synthetic circuits the toggle switch and the repressilator are published.
November 1978
Nobel Prize is given in Physiology or Medicine for the discovery of restriction enzymes.

Werner Arber, Daniel Nathans, and Hamilton Smith share the 1978 Nobel Prize "for the discovery of restriction enzymes and their application to problems of molecular genetics."

June 29, 1912
The term synthetic biology was coined by French biophysicist Stéphane Leduc

Further Resources

Title
Author
Link
Type
Date

ACS Synthetic Biology (ACS Publications)

Web

Synthetic Biology

Drew Endy

Lecture slides and notes

Synthetic Biology - A Primer

Paul S. Freemont (Editor),‎ Richard I. Kitney (Editor)

News

Title
Author
Date
Publisher
Description
Jennifer Ouellette
February 23, 2021
Ars Technica
Computer science pioneer Alan Turing first proposed the patterning mechanism in 1952.

References

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