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Designer crops

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Antony Evans, CEO of TAXA, describes the latest developments in plant genetic engineering that radically simplify the potential to create and test new genetic constructs with useful properties, such as plants with enhanced flavour or increased levels of vitamins.

What if you got your daily caffeine fix from an apple rather than a $5 Starbucks latte? Or if you could get omega-3 fatty acids from mashed potato instead of endangered fish? Or how about a blue strawberry, because well, just because.

All of these applications could be coming to your dining table in the not too distant future thanks to a suite of technologies developed by TAXA, a biotechnology company based in California, which facilitate metabolic engineering in plants, enabling the creation of new varieties with unique pathways enhancing flavour, colour or production of useful small molecules, like caffeine or vitamins. The technology is open for anyone to use, in contrast to the traditional agricultural biotech companies which keep inventions secret and proprietary.

TAXA’s ultimate vision is a world where bio-engineering is as easy and commonplace as mobile application development is today. Game-changing technologies, like genetic engineering, should not be the exclusive preserve of large corporations and a wealthy elite. To this end the TAXA platform is available to anyone in the world, irrespective of local licensing regulations on GM plants. All the work happens in our laboratory in California but it can be guided by anyone with an internet connection. Users can design genetic constructs, test their performance in plants and even order a stable line - without touching a pipette.

Technology trends
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What makes this possible is the convergence of several technology trends. The first is the dramatic reduction in the cost of sequencing technology illustrated in the chart below. This greatly increases the number of genes a genetic engineer has access to, opening up new applications and possibilities.

A related trend is the falling cost of DNA synthesis, the core input for today’s genetic engineer. Synthetic DNA allows improved performance of genetic constructs through techniques like codon optimisation and replaces the slow, tedious traditional process of cloning genes from their natural host.

The second trend is automation which reduces scientist lab bench time (and cost) and improves reliability and reproducibility. This trend is driven by Moore’s Law 1 and broader technological developments related to The Internet of Things. 2

A scientist can now get the kind of leverage previously available to computer programmers; once a protocol is developed and encoded it can be reused by anyone with an internet connection at very low cost, even those without the technical knowledge to understand the details. This enables operation at a higher level of abstraction, focusing on the design rather than technical details of how to implement the design.

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The third trend is the widespread adoption of technologies that allow less regulated paths for products to reach the market. As illustrated by the following chart, we are in the midst of the second wave of genetically engineered plants reaching the US market. This is  driven by use of the gene gun, which allows product developers to bring new genetically engineered plants to market without the cost, uncertainty and complexity of going through the USDA’s deregulation process.

Furthermore the FDA has a post-market approval process for the introduction of GM foods, with a voluntary process that has historically always been followed by developers but which is not obligatory. Putting this together with the USDA process offers the tantalising prospect of today’s genetic engineers being able to develop and bring to market a new product without years of regulatory approval requiring millions of dollars. While it’s unlikely that any product will receive widespread mass market acceptance without the FDA’s stamp of approval, this does allow bio-entrepreneurs to sell small quantities of new products direct to consumers to validate demand for the product before incurring significant regulatory costs. This ‘lean’ or ‘agile’ approach to product development lowers risk and should increase the range of products which make economic sense to develop.

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n addition to lower costs, the other feature of the second wave of GM plants in the market is who benefits from the engineered trait. The first wave of GM plants included traits designed to benefit the farmer and producer. Because this didn’t directly benefit consumers, it contributed to the backlash against GMOs that reduced the market potential of GM plant products. The second wave however includes traits that directly benefit the end user rather than the producer. This may lead to greater acceptance of the end products.

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The Glowing Plant, TAXA’s first product and the first genetically engineered organism funded on Kickstarter (the world’s largest funding platform for creative projects) 3, was developed with this in mind. The aim is to put genetically engineered glowing plants in people’s homes to change public reaction to genetic engineering: a child who grows up with a glowing plant in its bedroom isn’t going to be so afraid of it.

The TAXA platform has been specifically designed to enableanyone to undertake metabolic engineering of plants to create novel applications which directly benefit the end consumer. The platform has four pillars or components and users can pick and choose which techniques they need and which experiments to run in order to develop their specific application.

Protein Engineering
Optimising proteins in plants is hard, slow work; it can be significantly more efficient to first optimise your target proteins in bacteria, like E. coli. TAXA has two methods available for protein engineering, both of which work on entire pathways: random mutagenesis or a saturation scan. The key limitation here is the assay, of course.

Automated DNA assembly system
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The DNA assembly system is automated, which means no more nights in the lab working on cloning. It provides a library of standardised parts, including promoters, terminators and selectable markers, that allows anyone to rapidly and affordably design and assemble many combinations of target pathway genes for testing in vivo. Currently all of their parts are in the Golden Braid assembly system.4 Users can design their sequences using their favourite DNA editing software.

Transient experiments
Transient experiments are designed to enable rapid testing of a DNA construct without the expense of a stable transformation. This allows a relatively large number of constructs to be tested quickly and affordably. Again the key bottleneck is the assay.

Stable transformation
The TAXA platform generally uses the biolistic method for stable transformation though it does also use Agrobacterium methods, which are cheaper. While the biolistic method is slower and more expensive to generate a single plant, its key advantage is that – if care is taken with DNA parts used – the final product is immediately free for sale and distribution in the United States without requiring regulatory review. This saves years and millions of dollars from the budget for getting the product to market.

Conclusion
Looking further into the future, genetic engineering technologies are going to become even more important. Today the world produces more than enough calories to feed everyone on the planet, but sadly lots of people are starving. This is due to food waste in rich countries rather than current calorific output. By 2050 however, due to population increase, we will not have enough calories per person even before waste - and that’s without considering changing tastes in emerging countries as people get wealthier and start demanding more meat, which has a lower calories per acre footprint.

It is not really feasible to expand the amount of land devoted to agriculture without destroying what is left of the world’s forests. This means radical solutions are needed, either dramatically enhancing calories per acre or opening up new locations to grow plants, such as floating fields growing crops in the ocean. Genetic engineering is the only realistic technology we have to meet these radical challenges. The next few years are going to be an exciting time for plant engineering.

Antony Evans is CEO of Taxa Bio-Engineering, Suite 230, 665 3rd Street, San Francisco, CA 94107, USA.
If you have an idea you would like to see come to life or if you want to learn more about how our vision is taking root, so to speak, please contact us.
Web: http://www.taxa.com Email: antony@taxa.com

References

1. http://www.intel.co.uk/content/www/uk/en/history/museum-gordon-moore-law...

2. http://www.theinternetofthings.eu/what-is-the-internet-of-things

3. http://www.kickstarter.com/projects/antonyevans/glowing-plants-natural-l...

4. https://gbcloning.upv.es/

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