Top 10 Moments in Synthetic Biology 2018

The breathtaking pace of advancements in synthetic biology never slowed in 2018. To name a few highlights: major leaps forward were made in DNA data storage, CRISPR technology, plastic degradation, and microbial drug delivery. All this activity sparked record funding for companies in the field as investors saw continuing growth. This year also experienced its share of controversy when a Chinese researcher claimed to have created the world’s first genetically edited babies. The incident sparked a backlash in the scientific community and reaffirmed the need for careful oversight to sustain ethical standards and prevent harm to individuals. Nonetheless, this year’s abundance of activities in synthetic biology research, technology, and applications showed that the field is on track to drastically improve the world we live in.

Here are 10 exciting moments and advancements in synthetic biology for the year 2018:

1. Record Investment in Synthetic Biology Companies in 2018

Investment in Synthetic Biology companies trends upward. (Source: SynBioBeta)

As a result of advancements in cellular engineering, sequencing, and bioinformatics, the number of synthetic biology companies and amount of investment in the field is growing exponentially.

SynBioBeta in December outlined a record breaking total of $3.8 billion in venture funding to synthetic biology companies, more than double the amount registered in the previous year. Companies developing animal product alternatives, bio-based materials, AI platforms, and therapeutics were rewarded for their innovation and potential. Moderna Therapeutics, a developer of mRNA drugs to treat a variety of conditions and a stand-out in the industry, went public in early December, achieving the largest public offering to date for a biotech company, raising over $600 million. More moves in the same week showed increased funding to Zymergen ($400 million), Synthorx ($131 million), Synthace ($25.6 million), GenEdit ($8.5 million), and Elemental Machines ($9 million). These companies have an array of focuses including the use of AI, automation, nanoparticles, DNA synthesis, and software. This investment trend points to marked growth in 2019 driven by breathtaking innovation that promises to continue changing the world for the better.

2. Nobel Prize in Chemistry Awarded for the Directed Evolution of Proteins

Frances H. Arnold, PhD. (Source: California Institute of Technology)

We as humans have harnessed the power of evolution to create novel molecules for our own benefit. This year’s Nobel Prize in Chemistry was awarded to three scientists who initiated techniques using evolution as a tool to develop synthetic proteins.

Frances H. Arnold, PhD, the Linus Pauling Professor of Chemical Engineering, Bioengineering and Biochemistry at the California Institute of Technology and a member of Twist’s Scientific Advisory Board, received the award for conducting the first directed evolution of enzymes, a protein engineering technique that mimics the process of natural selection to steer enzymes towards a specific goal. Using this method, enzymes have been developed and used in the production of pharmaceuticals, renewable fuels, and more environmentally friendly chemical substances.

George P. Smith, PhD, a Curators' Distinguished Professor Emeritus of Biological Sciences at the University of Missouri, and Sir Gregory P. Winter, PhD of the MRC Laboratory of Molecular Biology in Cambridge, UK, shared the other half of this year’s Nobel Prize in Chemistry. They  developed an elegant method in 1985, known as phage display, where a bacteriophage – a virus that infects bacteria – is used to evolve new proteins. The phage display technique has been used in the directed evolution of antibodies, which are used as pharmaceuticals. This method has resulted in novel antibodies used to treat several autoimmune diseases and metastatic cancer.

3. Discovery of ScCas9 Enzyme Needing Just One G to Cut DNA, Opening Up CRISPR Editing to Huge Amounts of the Genome

CRISPR-Cas9 (Source: Adobe Stock)

CRISPR-Cas9 is a natural adaptive immune system found in a small fraction of bacteria and is able to perform precision cuts in DNA. Since its first reported use for editing mammalian cell genomes in 2013, numerous advancements have been made to improve the specificity and breadth of the tool.

In October, researchers at MIT, led by Joseph Jacobson, discovered that a Cas9 endonuclease from the Streptococcus canis bacteria (ScCas9) has a protospacer adjacent motif (PAM) - a specific DNA sequence downstream of the DNA editing site required for Cas9’s ability to cut DNA - of any two bases and only one guanine nucleotide (NNG), opening the window for almost 50% of genomic sequences to be edited. Currently, the most widely used variant of Cas9 is from the Streptococcus pyogenes bacteria (SpCas9) and has a PAM site of any base, followed by two guanine nucleotides (NGG). This requirement constraint limits the  CRISPR-SpCas9’s editing capabilities to approximately 9.9% of the genome. The discovery of ScCas9 increases the amount of potential genomic editing sites by five times, greatly expanding CRISPR’s utility.

4. Engineering of a Plastic-Degrading Enzyme

Plastic is defiling our environment and damaging ecological havens. (Source: Adobe Stock)

The build-up of plastic waste in our oceans and landfills is due to plastics’ non-biodegradable chemical structure. An exciting discovery in 2016, led by a team of researchers at Kyoto Institute of Technology, revealed that a bacteria, isolated from outside of a plastic bottle recycling facility had evolved an enzyme - PETase - to degrade the plastic polyethylene terephthalate (PET). PETase has the potential to be revolutionary in plastics recycling, but is too slow at breaking down PET for use in large scale recycling.

This year, a team of scientists from Britain's University of Portsmouth and the U.S. Department of Energy's National Renewable Energy Laboratory, characterized the 3D structure of PETase, and also engineered changes in the enzyme that greatly increased the rate at which it breaks down PET. They also showed that PETase breaks down additional types of plastic. This work opens the door for the development of a new era of plastic-busting enzymes, and takes us a step closer to repairing the damage caused to our world by plastic.

5. First Report of DNA-Based Random Access Memory (RAM)

The density and longevity of storage using DNA is attracting attention from a variety of innovators. (Source: Adobe Stock)

The explosion of data across all industries and the need to store that data  - estimated by IDC to reach 163 zettabytes (trillion gigabytes) generated and stored per year by 2025 - has led to the exploration of novel methods for storing large amounts of data. In recent years, there have been great advancements in the use of DNA, the natural data storing molecule of life, as a replacement for traditional long term data storage materials such as tape, which degrades quickly, or memory grade silica, which is estimated to run out by 2040. In 2016, Twist Bioscience announced a collaboration with Microsoft and the University of Washington, focused on the use of DNA as a data storage device.

In February 2018, researchers from Microsoft and University of Washington published a study in which they not only archived record breaking volumes of data in DNA, but also stored the data in a format that models random access memory (RAM) for the first time. Previously, if access to a single DNA-stored file was required, the entire pool of DNA would have to be read by next-generation sequencing. To achieve single file access, researchers encoded unique sequences flanking each file as a “memory address.”

6. Functional Yeast Created with Only One ‘Super-Chromosome’

Three-dimensional view of chromosomes (Source: Adobe Stock)

What is the point of having multiple chromosomes? Scientists speculate  that an organism’s chromosome count is down to chance, and not an underlying rule of nature. To illustrate this point, researchers from the Chinese Academy of Sciences performed a complex genetic surgery with CRISPR on the 16 chromosomes of brewer’s yeast to create one ‘super-chromosome.’

The group used successive CRISPR genome editing in live yeast, resulting in end-to-end fusion of all 16 chromosomes and deletion of centromeres. Amazingly, even though there were significant structural changes to the DNA, the single-chromosome and wild-type yeast cells had nearly identical transcriptome and similar phenome profiles. While the giant single chromosome can support cell life, the strain shows reduced growth and viability. This synthetic biology study demonstrates an approach to explore eukaryote evolution, and help scientists understand why organisms split their DNA over chromosomes.

7. Live Bacterial Therapeutic Successful in Phase 1/2 Trials for Treatment of Phenylketonuria

Scientists are taking a giant leap forward in the concept of a probiotic pill and engineering bacteria as a treatment for disease. (Source: Adobe Stock)

When a person takes a probiotic pill, they can swallow billions of bacteria with the hope of maintaining a healthy gut. These bacteria are natural to humans and help with food digestion and vitamin production, but scientists are taking the concept a giant leap forward and engineering bacteria as a treatment for disease.

In September 2018, Synlogic, a biotechnology company combining synthetic biology and the microbiome, reported positive Phase 1/2 clinical trial data for Phenylketonuria (PKU) patients treated with an engineered bacteria, called SYNB1618. SYNB1618 is engineered from Escherichia coli Nissle, a widely studied strain of E. coli that has been shown to help maintain healthy digestion and is currently found in many probiotics. Scientists at Synlogic engineered E. coli Nissle to produce enzymes that break down the amino acid phenylalanine, which builds up and causes neurotoxicity in patients with PKU. The positive trial results are an exciting advancement for the field of bacterial therapeutics, and promise progress for patients suffering with PKU.

8. High-Throughput Foundry Opened for the Rapid Genetic Engineering of Mammalian Cells

A Ginkgo Bioworks researcher using state-of-the art equipment in one of the company’s foundries. (Source: Ginkgo Bioworks)

As the focus on biologics and cell therapies grows rapidly, cell engineering capabilities must keep up. Companies such as Ginkgo Bioworks, the organism company, are stepping up to the plate by offering high-throughput services for cell engineering. Ginkgo Bioworks was originally known for automated, high-throughput manufacturing of engineered bacteria and yeast, but this year has expanded the company’s capabilities to include engineering of mammalian cells. Bioworks4 is Ginkgo Bioworks’ newest foundry, which opened in October 2018, applies its automated, high-throughput process to the exclusive engineering of mammalian cell genomes.

The foundry is accelerating the process for developing products so that a biological engineer working with the foundry can accomplish nearly 25 times more than was possible using traditional by-hand methods, a number that continues to increase as Ginkgo grows and foundry technologies improve. Bioworks4 is equipped with capabilities from gene editing to systems-level analysis and has the unique ability to rapidly prototype and test new cell lines in higher throughput, with accelerated timelines. These engineering capabilities are fueled by DNA supplied by Twist Bioscience. With the ability to test more engineered cells with much higher efficiency, the industry will be able to develop new biologic tools and therapies at a much faster pace.

9. Ethical Outcry Over Report of CRISPR-Engineering of Genes of Babies

The announcement of CRISPR-engineering of genes of babies set off a strong backlash in the scientific community. (Source: Adobe Stock)

Chinese researcher He Jiankui shocked the world this year when he announced that twin girls had been born from embryos engineered using the gene editing tool CRISPR. Using in vitro fertilization, Jiankui attempted to delete the CCR5 gene from two female embryos using CRISPR-Cas9. According to previous research, deletion of the CCR5 gene has the potential to eliminate the risk of contracting HIV, a disease that is commonplace in parts of China. The embryos were then reportedly implanted into the womb of their mother, who gave birth in November 2018. As of yet, editing of the twins’ genomes has not been confirmed by peer review. Jiankui, an associate professor in the Department of Biology of the Southern University of Science and Technology in Shenzhen, China, received Ph.D. degree in Biophysics from Rice University and worked as a postdoc fellow at Stanford University.

The announcement set off a strong backlash in the scientific community as researchers were quick to publicly condemn the act as unethical. While such research raises many important ethical concerns, the calls to action against such experiments may reinforce vigilance.

The National Academy of Sciences (NAS) and National Academy of Medicine (NAM) formed a science advisory group in 2017 that proposed a recommendations for human gene editing. The NAS/NAM report supports human gene editing in specific, limited situations, and laid out specific guidelines, and seven main principles to guide the practice of human genome editing: promotion of well being, transparency of research, due care in clinical research, responsible science using high standards, respect for persons, accessible research, and transnational cooperation. Twist Bioscience endorses the guidance outlined in the NAS/NAM report and strongly agrees that human gene editing must be conducted responsibly.  Following Jiankui’s announcement, the presidents of NAS and NAM  expressed concern about his work. “The events in Hong Kong this week clearly demonstrate the need for us to develop more specific standards and principles that can be agreed upon by the international scientific community,” NAS president Marcia McNutt and NAM president Victor Dzau said in a statement.

10. Winning iGEM Teams Show Off Amazing Research at the Worldwide Jamboree

This year’s iGEM Giant Jamboree attracted 340 teams. (Source: iGEM.org)    

Every year since 2004, the Genetically Engineered Machine (iGEM) Foundation has held a competition in which multidisciplinary teams work throughout the summer to build genetically engineered systems using standard biological parts called BioBricks. The competition culminates in a Giant Jamboree where participants present their work, and awards are given. This years’ competition had 340 teams - the most ever - from 80 different countries. Below are the grand prize winners in each category for 2018:

The grand prize in the high school division was granted to Great Bay China, for development of mCATNIP, a biosynthetically manufactured version of nepetalactone - the active ingredient in catnip. The team then worked with local animal rescue teams to create the “kitty wonderland,” which uses mCATNIP within a shelter for cats to attract and hold feline visitors while notifying local authorities. This innovation was developed to address the growing feral cat problem currently facing parts of China.

The grand prize in the undergradate division was granted to Valencia UPV, from Spain, for development of a robotic bioengineering device, which serves as an all-in-one synthetic biology lab called Printeria. The fully automated system takes a researcher’s genetic pathway designs as input, and outputs a genetically engineered organism. Modules in the machine work on each part of the experimental workflow, allowing the researcher to focus on experimental design over performance.

The grand prize in overgraduate division was granted to Team Marburg, from Germany, for accelerating metabolic engineering by designing a toolbox to engineer Vibrio natriegens, the world’s fastest growing bacterium. The team developed three unique strains of V.natriegens and established protocols for cloning, protein expression, and protein interaction studies, achieving an astounding 12-hour workflow for a complete cloning cycle. Additionally, the team established the first synthetic pathway in V.natriegens to produce the biodegradable polymer 3-hydroxypropionic acid.

Read more about the 2018 iGEM Grand Prize winners and technology here: iGEM 2018 Grand Prize Winners: The Next Generation of SynBio Innovators

Looking back on 2018, the year proved to be one of astounding growth in synthetic biology research techniques, clinical use, and funding, building upon the nobel prize winning concepts awarded this year. Biological advancement is a collective effort where scientists armed with old and new knowledge come together to create novel tools, techniques, and medications, and this year proved to be no different. We are living in exciting times and on track to elevate quality of life for humans, and all life on Earth.

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