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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 to redesign systems that are already found in nature to have new abilities.

Synthetic Biology Fundamentals

Synthetic biology involves designing, engineering, and building biological systems using standardized biological parts. Standardized biological parts include DNA fragments that code for proteins and DNA elements that regulate transcription. There are common techniques for identifying, isolating, storing and manipulating these biological parts. The generation of customized cells with fully synthetic genomes is another area of synthetic biology.

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DNA 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.

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

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 bottoms-up approach to put together well-characterized genes and proteins to produce synthetic gene circuits that perform desired functions.

Transfection of Nucleic Acids

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

Optogenetics

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.

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).

Theoretical biology and artificial life
Whole genome engineering
  • Genome Project-write (GP-write) is an open international research project that plans to reduce 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.
  • Minimal bacterial genome
  • Synthetic Yeast 2.0
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 the access to renewable and affordable sources of feedstock, as well as 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 we otherwise obtain 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. However, 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 improve 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, 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.

Biosensor Companies

Synthetic Tissue Development

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 construction of self-assembling structures would use the following sequence: 1) form a pattern, 2) change gene expression, 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.

Tissue Engineering Companies

Engineered Living Materials

Engineered living materials (ELMs) are engineered materials made of living cells able to form or self-assemble material or modulate the functional performance of 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 towards producing engineered living material include 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 material:

  • 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.
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

"Omics" Projects and Biological Atlases

Technical Roadmaps

Standardization
Facilitating access to DNA sequences
Blockchain and biology

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.

For 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. Information must be accessible to patients, physicians, laboratory scientists, logistics companies, supply chains, and infusion centers. For blockchain companies in this area see subsection under "Companies" heading below.

Conferences
Organizations and projects
Startup Incubators and Accelerators
Nonprofits
Companies
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 product 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 plastic. 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).

Bioplastic companies

Biological control system
Biopharma and health

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 contributor to loss of tissue and organ function over time in aging and age-related disease.

Autoimmune diseases

Cancer

Immunotherapy

Vaccines and infectious disease treatments

Other areas

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).

Biomanufacturing companies

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 companies

Biosecurity companies

Blockchain

Blockchain applied to tracking and security of biological data

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.

Chemicals production
Food and agriculture
Gene/Genome synthesis
Genome/protein engineering
Lab tools
Lab space
Organism Engineering
Phage engineering

Phages are engineered for use as phage therapies as antimicrobial agents and also for delivery of drugs and vaccines. Phages can also be engineered to assemble new materials.

Research labs
Federal organizations
Software
Venture Capital
Biosafety Organizations

Timeline

May 2, 2019
One of NHGRI's goals is to promote new technologies that could eventually reduce the cost of sequencing a human genome of even higher quality than is possible today and for less than $1,000.

People

Name
Role
LinkedIn

Christina Smolke

Professor, Stanford

Jason Kelly

Co-founder and CEO, Ginkgo Bioworks

Documentaries, videos and podcasts

Title
Date
Link

The GeneMods Podcast

July 2017 - Present

Companies

Company
CEO
Location
Products/Services

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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