Using Synthetic Biology to Engineer Membrane Proteins
Synthetic DNA is changing the way research is performed, allowing scientists to focus on performing their experiments and accelerating their discoveries.
2016 has been a fantastic year for synthetic biology! Here is our roundup of the year’s top moments, innovations, and improvements.
The Genome Project – Write Launches
In 1990 the quest to sequence the human genome was launched. Completed in 2003, it has become the major driver of modern biological discovery, initiating a new era of genomic innovation. Having access to a complete human genome sequence allows researchers to attribute human diseases to their genetic hallmarks, changing diagnostic and personalized medicine forever. Twenty-six years later, the journey continues with the announcement of a new mission – “Genome Project – Write” (GP-Write).
As stated in the GP-Write’s proposal publication, “the capability to construct DNA sequences in cells is mostly limited to a small number of short segments, restricting the ability to manipulate and understand biological systems.” With $100 million in initial funding, GP-Write will strive to achieve genome scale synthesis, engineering an entire synthetic human genome within a cell line – with the objective to comprehensively understand the blueprints for life, and responsibly study biological processes and disease.
While the media reacted unfavorably to the initial closed-meeting session, the organizers behind GP-Write have maintained complete transparency about the project’s purpose, even prior to initiating any activity. Responsible innovation will play a huge role in the project, which according to the GP-write website, will include “identifying common goals important to scientists and the public through timely and detailed consultation among diverse stakeholders.”
Find out more on the project’s website.
According to figures from SynBioBeta, 2016 has been a booming year for the SynBio industry in the United States. At last count, North America is now home to 192 SynBio companies, backed by a record-shattering $830 million of private investment within the last year – that’s equivalent to approximately 25% of all global synthetic biology investment in the previous six years! Twist Bioscience is proud to have raised $61 million in a Series D financing this year as well.
SynBioBeta go into further detail in their blog post.
C2c2 is CRISPR for RNA
It’s been four years since the first studies were published describing CRISPR-based gene editing, and it is still a hot topic in SynBio circles. However, CRISPR’s throne may soon be in jeopardy. This year, some alternative CRISPR-esque sequence-directed genetic modification systems have been discovered – one being the enzyme C2c2.
By searching databases for protein families similar to the Cas9 enzyme (the “scissors” in the CRISPR system), researchers discovered C2c2. This system is guided by an RNA molecule to a cut site in the same manner as Cas9. Instead of being guided to DNA, C2c2 prefers to bind and cut RNA. Twist Bioscience synthesized the oligo pool used to characterize C2c2’s mechanism of activity in this study. With this RNA targeting system, proteins could be turned off without ever touching the genome. Accordingly, cell lines that mimic disease states could be created transiently, without the need for cell line engineering.
Find out more in the Broad Institute’s news article.
Feeding the World – Plants Engineered for Better Photosynthesis
The world’s population continues to grow. Unfortunately, worldwide farmable land is declining from forces like climate change, pollution, and soil erosion, which raises concerns about the future of food availability.
One problem is that plants are not built for food production, but for reproduction. Efforts focused on selective breeding and crop engineering over the past 60 years have greatly improved yields – though until now, a plant’s efficiency when converting sunlight into energy by photosynthesis has been a bottleneck.
A collaboration between the University of Illinois, Urbana and the University of California, Berkeley showed that tobacco plants engineered to express “shade response” proteins from the mustard Arabidopsis thaliana produce up to 20% more biomass. If this simple system was used in crops, farmers would be able to grow more food per plant, an important step towards ensuring that the world’s growing population can grow enough food to eat.
Read more in a press release by the journal Science.
CRISPR Achieves Clinical Milestone: First Trial Use in Cell Therapy
Last year, we highlighted work by Junjiu Huang and colleagues of Sun Yat-sen University in China, who published the first experiments using CRISPR to edit the genome of a non-viable human germ line cell. This move was so controversial it prompted an international summit of 400 experts to discuss the responsible use of gene editing. The summit concluded that while germline engineering is irresponsible, a case can be argued for the use of gene editing technologies in the treatment of otherwise untreatable diseases.
This year, groups from both the U.S. and China received approval from their respective ethics and regulatory committees to begin human trials of CRISPR-engineered, targeted cell therapies. A group led by oncologist Lu You of Sichuan University were the first to initiate the trial and is currently treating a patient with aggressive lung cancer for whom all other therapies have failed.
The treatment involves isolating the patient’s T-cells, deleting a gene called PD-1 that normally stops the immune cells from attacking cancer, and re-injecting the edited cells into the patient. The first U.S. trial, scheduled to begin in early 2017 at the University of Pennsylvania, will focus on the safety of CRIPSR in humans, rather than treatment of a specific disease. Results of both studies are anticipated in 2017.
Microsoft and the University of Washington Store Record Amount of Digital Data on DNA
DNA no longer has applications solely in biology – Microsoft, Twist Bioscience, and the University of Washington announced a collaboration to utilize DNA to encode, store, and archive digital data.
Currently, data archives are kept on large flammable tapes that need to be replaced every 10 years or so. If digital data would be encoded in DNA, in the same way genetic information is encoded in nature, huge amounts of digital information could be stored in small tubes for tens of thousands of years.
Recent, impressive advances have been made in the field. For example, with DNA synthesized by Twist Bioscience, researchers at Microsoft and the University of Washington encoded and then decoded a record 200 MB of data, including an entire music video for the song “This Too Shall Pass” by the band OK Go. This project recently won Popular Science’s “Best of What’s New” award. The exponential growth in digital data storage is driving technological breakthroughs in DNA synthesis that looks to Nature for inspiration to meet these capacity requirements.
NgAgo Could Be a Better CRISPR – If it Works
Also in the gene editing spotlight is NgAgo – a system that has caused substantial controversy in the SynBio community this year.
Unlike CRISPR, NgAgo uses DNA instead of RNA to guide an enzyme from the Argonaute family to a desired genetic cut site. When researchers want to use NgAgo they only need to synthesize small, cheap oligonucleotide guides — with CRISPR this process is more complex. This new system also appears to exhibit unprecedentedly high editing accuracy.
NgAgo looked set to take the gene editing throne from CRISPR.
However, very soon after its discovery, researchers around the world challenged the original paper’s repeatability. Alternative reports quickly arose suggesting the system only blocks gene expression and does not cut the DNA. NgAgo’s controversy culminated in a 20-author paper in which all authors report their failure to get NgAgo to cleave DNA in mammalian cells. However, Han Chunyu, project leader on the initial NgAgo announcement, says this paper “provides [them] some clues as to why others are having problems.” His group should be publishing solutions in a new article due at the very end of 2016.
It’s important that the scientific method is in play, with diverse groups looking to replicate the same experiments to either confirm or reject the original study. The entire scientific community benefits through this system of peer review, and whatever the result, NgAgo will certainly be one to watch in early 2017!
Oxitec Mosquitoes Decrease Incidence of Dengue Fever
Mosquitoes are the biggest transmitter of lethal disease in the world. Synthetic biology company Oxitec hopes to push the population of one of the planet’s most dangerous organisms into decline by releasing a genetically engineered mosquito variant.
Their “Friendly™ Aedes” mosquitoes are all males containing a lethal genetic trait that activates upon reaching adulthood. On release into the wild, these male mosquitoes mate with females and pass the lethal gene to their progeny, causing population declines. Open field tests in multiple locations around the world showed an over 90% reduction in local mosquito populations.
In 2016, Oxitec announced that the release of their Friendly™ Aedes mosquitoes in Piracicaba, Brazil caused a 91% decrease in recorded dengue fever cases. Since that time, Oxitec has opened a large-scale mosquito production facility in Brazil. Additionally, the FDA found no significant environmental impact caused by the release of Friendly™ Aedes into the environment.
Find out more about Oxitec’s pursuit to significantly lower the worldwide impact caused be mosquito-borne disease on their website.
SynBio Competition iGEM Sees its Greatest Ever Number of Competitors This Year
Three thousand young synthetic biologists flocked to Boston this year to compete in the international Genetically Engineered Machine (iGEM), an increase over last year’s attendance of 2,700. iGEM is a global synthetic biology competition that allows the next generation of researchers to develop innovative projects, collaborate across the world, and engage with the public about their work.
Some great projects from this year’s competition were 3D bioprinters to print human organs, bacteria that can survive extreme conditions thanks to proteins from a curious organism called a “water bear”, and insecticides made from spider venom.
Read more in our round up of iGEM on our blog.
SynBio Company Ginkgo Bioworks is the World Leader in the Utilization of Synthetic DNA for the Second Year Running After Significant Growth
DNA synthesis capacity has exploded exponentially in the past two years. Synthetic biology company Ginkgo Bioworks maintains world leadership in exploring sequence space, utilizing 100 million bases of DNA in 2016.
Ginkgo used this DNA in their biofabrication suite “Bioworks 1”. Within Bioworks 1 Ginkgo develop new organism strains for the industrial production of useful scents and flavorings in a high-throughput manner. This year, Ginkgo announced they would be partnering with Twist Bioscience again to receive an additional 300 million bases through 2017.
This DNA will be used to power Ginkgo’s significant growth, enabling their rapid prototyping of new industrial organism strains. A lot of this work will be performed in Ginkgo’s new state-of-the-art biofabrication facility “Bioworks 2”.
The Moon Parka and Other Fashionable SynBio
Spider silk is stronger than steel by weight, it is tougher than Kevlar®, and lighter than carbon fiber – it’s a holy grail material for wearable protection. Its downfall, however, comes from the difficulty of cultivation, requiring almost 15,000 spiders to spin just one ounce of thread.
Japan-based synthetic biology company Spiber has a solution: replace spiders with bacteria engineered to produce a spider silk protein called a spidroin. Instead of spinning silk, Spiber generates it synthetically – a process the company has been developing since 2008.
With an unprecedented leap in materials science, Spiber developed a synthetically-derived version of spider silk called QMONOS™. Spiber partnered with outdoor apparel company North Face to announce the Moon Parka – a coat made with the QMONOS™ material. With much fanfare, the Moon Parka prototype was on display at the flagship North Face store in New York earlier this month. Billed for release in 2017, the Moon Parka is expected to cost a cool $1,000, but as the world’s first wearable piece of spider silk, it is a statement: SynBio is set to take its place in the multi-trillion dollar textiles industry.
In addition to the Spiber/North Face partnership, other collaborations between clothing and synthetic biology companies were announced this year. In May 2016, an up-and-coming U.S.-based company, Bolt Threads, announced a partnership with outerwear company Patagonia. Adidas also recently unveiled a partnership with the company AMSilk to produce the Futurecraft Biofabric shoe using AMSilk’s Biosteel® technology. These projects further solidify SynBio’s place among the textiles industry.
Find out more about the Moon Parka on Spiber’s website
This has been a great year for synthetic biology, with many exciting advancements and innovations. As we toast to the end of 2016, we look forward to many great things synthetic biology will bring us in 2017!
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