Top 10 Moments in Synthetic Biology 2017

The year 2017 has been another great one for synthetic biology. This year has seen some big steps towards the realization of the humanity-benefiting promise of synthetic biology, with many new emerging applications. CRISPR-based technologies have seen significant advancement, covering the media with new discoveries. Synthetic biology’s application in healthcare is also seeing great exploration. Also, funding raised by industry- leading synthetic biology companies continue to trend towards beneficial application-focused investments from textiles to pharmaceuticals.

What are our favorite moments of the year? We’ve compiled our top 10. ¡Disfrute!

 





CRISPR has revolutionized synthetic biology. Its elegance and precision make gene editing procedures simple and reliable, presenting new opportunities for biological research and technological development. Some of the most exciting prospective CRISPR applications are in the treatment of genetic diseases. Many debilitating diseases, such as Duchenne muscular dystrophy, cystic fibrosis, Huntington’s disease, and several forms of cancer have been considered incurable because they are directly linked to inherited genes. The precision of CRISPR’s genome editing in living organisms is powerful and many genetic illnesses are potentially treatable in the near future.  

This year, the first group of CRISPR-based clinical trials for inherited diseases have been proposed, with starting dates likely to be announced in the next year. CRISPR Therapeutics submitted a clinical trial application to European regulators proposing a clinical trial of a gene editing therapy for beta (β)-thalassemia and sickle cell disease. Clinical trials will soon commence in China to treat HPV-infections that can cause cervical cancer.

Genetic diseases that originate from clearly defined mutations are the most attractive targets for CRISPR-based gene therapy. Nevertheless, the CRISPR human trials initiated this year mark a significant advance toward clinical adoption of these novel gene therapies. The parallel development of CRISPR variants and delivery methods is also widening the range of CRISPR’s potential clinical applications.





In a collaboration of Twist Bioscience, Microsoft, and the University of Washington, the digital data of live versions of “Smoke on the Water” and “Tutu” recorded at the Montreux Jazz Festival were encoded into the four bases of DNA. This project marks the first time data has been stored in DNA at archival quality.

Data can be stored in DNA by converting its binary code into the four bases that compose DNA, and then with high throughput, next generation DNA synthesis like that provided by Twist Bioscience, the data can be encoded chemically as a sequence of nucleotides. By 2040, it is predicted the amount of data humans will have created will surpass the amount of memory grade silicon available, and long-term data archives will be a necessity. Current archives store data on tapes, requiring huge infrastructure investment as the archived data needs to be copied every 10 years to fight degradation. DNA used to store data will last over 10.000 years, and an absolute upper limit of a zettabyte of data can be stored in one gram DNA. This collaboration is a milestone in data science, and suggests DNA will be the data storage medium of choice in the coming years.





Spider silk is one of the strongest yet softest materials on Earth, but unlike the similar, less resilient material made by silkworms, it has not been adopted as an industrial material. The main barrier preventing the industrial production of spider silk has been that spiders are not able to be farmed at the massive scale required for their silk to be economical.

Fear not — biotechnology startup Bolt Threads found a workaround. Using gene editing techniques now widely available because of advances in synthetic biology, the company engineered yeast to produce spider silk proteins as a metabolic byproduct. After gathering these proteins, a machine spins the loose fibers into fine silk, which can then be woven into fabric.

Bolt’s first limited run of spider silk neckties was available for purchase earlier this year, and efforts are underway to increase manufacturing capacity and produce a wider array of products. At the same time, other companies are prototyping spider silk garments: Japanese spider silk manufacturer Spiber is collaborating with The North Face to produce a parka, and Adidas is developing a shoe made in part from similar bioengineered textiles.

 





Cas9, the endonuclease enzyme that cuts DNA at the precise location specified by the rest of the CRISPR complex, has been visualized performing its DNA-cutting function in real-time by a team of researchers in Japan. Using a high-speed atomic-force microscopy to produce atomic-scale scans of the heights of sample surfaces in rapid succession, the researchers were able to create a movie of Cas9 in the act of DNA cleaving.

Further, the researchers used their visualization technique to study various properties of Cas9. They were able to study the kinetic behavior of Cas9 with and without RNA attached, and observe that RNA binding stabilizes the structure of Cas9 and prevents it from flexibly adopting any of numerous possible conformations. The researchers were also able to study the diffusion of the Cas9-RNA complex through the DNA environment, from which observation they could elucidate properties of Cas9’s “DNA interrogation” – the process by which Cas9 finds its target site among the entire DNA molecule.

Visualizing Cas9 at this unprecedented resolution advances CRISPR’s clinical potential. For CRISPR-based gene editing to be used in medicine, it is crucial to fully understand the activity of Cas9, to address both safety and engineering concerns. By observing Cas9 with this fine level of detail, researchers can refine the current model of how the enzyme cuts DNA.





All life as we know it has its form and function encoded in the four nucleotides of DNA: A, T, C, and G. From the two base pairings formed by this four-letter code, messenger RNA is transcribed. The sequence of RNA is then translated into proteins, which within the cell undergo chemical reactions required to keep us alive. In this process there is a natural flow of information, a flow that if modifiable, could lead to the formation of new proteins containing parts that are non-natural, paving the way for the engineering of novel functions.

For the first time, a collaboration of synthetic biologists from the Scripps Research Institute and protein therapeutic discovery company Synthorx have succeeded in modifying life’s information highway to create a semi-synthetic organism with an expanded nucleotide set. Their system incorporated a new base pair into the genome of their organism, denoted as X and Y. The organism then recognises this base pair and uses it to encode the unusual, non-natural amino acid p-azido-l-phenylalanine, and incorporates it into an encoded green fluorescent protein. Such technology could prove powerful in the protein pharmaceutical industry, allowing a new route to engineer novel functionality into proteins. For example, the addition of an azido functional group allows for highly reactive chemistry, making the attachment of a drug or other molecules of interest more effective.

 





Zika virus is a high-profile disease and the subject of international alarm, even among other mosquito-borne tropical diseases, because of its particularly harmful effects in rare cases. In adults, Zika can cause significant neurological effects, such as Guillain-Barré Syndrome. Children born to mothers infected with Zika can be afflicted by microcephaly and other birth defects. 

The steadily increasing rate of international travel, along with mass travel events such as the 2016 Brazil Olympics, has raised the global urgency of Zika research over the last several years. Despite several large research efforts, no vaccines have advanced far enough in development to be deemed safe in humans and effective for Zika prevention – until this year.

U.S. scientists at the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, published Phase 1 clinical trial results suggesting that a new gene-based Zika vaccine is safe and successfully induces an immune response in healthy adults. Their vaccine utilizes synthesized Zika virus surface proteins to provide the body’s immune system with material for combating a viral infection. Phase 2 trials are currently underway to further investigate the new vaccine candidate’s safety and efficacy.





This year’s international Genetically Engineered Machine competition (iGEM) was the biggest in the event’s history, hosting over 300 teams, and totalling 5.000 students across every continent. Each year, prizes are given out to teams who conducted some of the most impressive projects, with the grand prize winners able to take home the coveted iGEM brick trophy. However, there is one prize that stands out - the Chairman’s Award. This award is chosen by iGEM Chairman Randy Rettberg, and is given to a team who truly embodies iGEM’s core values of integrity, effort, honesty and excellence. As a result, the award isn’t given out every year — the last team to win was the Indonesian team Sumbawagen in 2014.

However, 2017’s iGEM was something special, as two teams picked up the Chairman’s Award: Ashesi University Ghana and Georgia State University. Georgia state caught the Chairman’s eye for their consideration of accessibility in STEM to those with disabilities, and their work to make synthetic biology open and exciting for children attending a school for the deaf and hard of hearing. They even had ASL in their presentation at the event to be inclusive of those they worked with throughout their project. 

Ashesi Ghana were commended for their efforts in solving the real and local problem of illegal mining. Their team was composed of engineers, not synthetic biologists. When they didn’t have lab equipment, they just used their engineering expertise to build it for themselves. “We as a team have gained an introduction to a new field,” said Claude-Noel Tamakloe, one of the team’s members. “We have the ability to redefine the career paths we have chosen and this serves as the foundation to the birth of new developments in this field of science in our homeland, Ghana.” Both winners defined this year’s iGEM competition and their work is indicative of huge steps towards a global, accessible and democratized synthetic biology

3) Improvements to Single-Base-Pair Editing Demonstrated 



 

A team of researchers from MIT and Harvard described a new technique to edit single DNA base pairs. The researchers engineered an enzyme called adenosine deaminase to transform A-T pairs into G-C pairs, to complement the enzymes naturally-induced mutation 

 from G-C to A-T.

Previously known CRISPR-based gene editing methods involve single- or double-stranded DNA breaks, whereby endonucleases would sever DNA strands to allow for the deletion or insertion of new genetic material. These DNA breaking methods, although highly precise, create opportunities for errors to occur in the DNA-rejoining process. By editing single base pairs without inducing any strand breaking, the possibilities of rejoining errors are eliminated, closing one possible entry point for deleterious off-target effects.

Many genetic diseases, such as cystic fibrosis, sickle cell anemia, and Tay-Sachs disease are attributable to mutations in single base pairs. The ability to correct these point mutations with high-precision marks a significant advance toward clinical therapies for genetic diseases.

 





B-cell acute lymphoblastic leukaemia (ALL) is the most common cancer in children, affecting around 3.100 patients under 20 years old in the U.S. each year. ALL is a disease affecting lymphocytes, an immune cell normally found in bone marrow. Blood tests of ALL patients show large numbers of faulty lymphocytes in their blood, and an impaired ability to produce normal red and white blood cells. Current treatments are chemotherapy and radiotherapy, causing remission in 85 percent of patients. 

For those who don’t respond to treatment, or those who enter relapse, a second option has become available this year. Tisagenlecleucel, marketed as Kymriah™, produced by Novartis with original research by the University of Pennsylvania, is the first FDA-approved therapy that uses a patient's own engineered T-cells to fight any disease. The patient’s T-cells cells are taken and engineered with the genetic information allowing them to target and destroy cancer cells before being infused back into the patient. The treatment was first used on a six-year old girl with an aggressive relapsed form of ALL - she is alive and well today, six years later. Of the 63 patients in the clinical trial, over 80% entered remission.

In comments in an FDA press release, Scott Gottlieb M.D., FDA commissioner stated, “We’re entering a new frontier in medical innovation with the ability to reprogram a patient’s own cells to attack a deadly cancer. New technologies such as gene and cell therapies hold out the potential to transform medicine and create an inflection point in our ability to treat and even cure many intractable illnesses.”

 





Synthetic biology market analysts SynBioBeta are reporting that 2017 is on track to be yet another record year for growth in synthetic biology, as the figure for total investment is pushing $1 billion. Early this year SynBioBeta announced their own partnership with venture capital fund Data Collective to start a venture fund solely aimed at synthetic biology, providing seed and pre-seed funding. This year’s investment hard-hitters include Ginkgo Bioworks ($100 million in a new partnership with Bayer, and $275 million in series D funding), Editas medicine ($90 million stock offering), Autolus ($80 million series C funding), and Twist Bioscience ($60 million raised). This year continues the same trend as seen in 2016 with investment in innovative applications and many of the top money raisers producing synthetic biology derived products.

After such an innovative year of synthetic biology in 2017, what can we expect in 2018? We’re sure synthetic biology will continue to fulfil its promise of delivering world-changing applications. Also, as the barriers to access synthetic biology are continually being brought down by innovation, for example through next generation DNA synthesis like that provided by Twist Bioscience, expect to see increasing numbers of synthetic biology applications hit the market. With it should come greater investment, advancements in preclinical and clinical research with CRISPR and other tech, new proof of concept studies moving towards novel commercial applications and overall, expect another year of rapid growth in the synthetic biology space.