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Topic 1: New technological developments in synthetic biology since the last meeting of the Ad Hoc Technical Expert Group

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Some synbio papers [#9365]
Dear all
It is not always obvious to me if an organism is the result of synthetic biology or if its just a conventional genetically modified or genome edited organism, but below you will find some article listed that might fit in.

Engineering photosynthesis
Scientists within the Realizing Increased Photosynthetic Efficiency Project has engineered a shortcut for photorespiration, which increased the yield with up to 40 percent. In this study tobacco was used. In another article published a month later scientists had engineered a shortcut for photorespiration in rice, resulting in 27 percent yield increase. 
• Synthetic glycolate metabolism pathways stimulate crop growth and productivity in the field. South et al, Science Vol. 363, Issue 6422, eaat9077; Realizing Increased Photosynthetic Efficiency: https://ripe.illinois.edu/
• Engineering a New Chloroplastic Photorespiratory Bypass to Increase Photosynthetic Efficiency and Productivity in Rice. Shen et al, Molecular Plant 12, 199-214, February 2019.

De novo domestication
With genome editing scientists can accelerate domestication of wild plants without losing valuable traits that has been lost during 1000 of years of domestication and breeding. This is exemplified by three recent papers on tomato and Physalis.
• De novo domestication of wild tomato using genome editing. Zsögön et al, Nature biotechnology, published on line 1 October 2018; doi.1038/nbt.4272
• Domestication of wild tomato is accelerated by genome editing. Li et al, Nature Biotechnology, published online October 1, 2018, doi:10.1038/nbt.4273
• Rapid improvement of domestication traits in an orphan crop by genome editing. Lemmon et al Nature Plants. Published online October 1, 2018. doi: 10.1038/s41477-018-0259-x

Gene drive
A paper published last year shows complete suppression of a Anopheles gambie population. In a paper published recently scientists used gene drive on mice.
• A CRISPR-Ca9 gene drive targeting doublesex causes complete population suppression in caged Anopheles gambiae mosquitoes. Kyrou et al, Nature Biotechnology published online 24 september 2018; doi:10.1038/nbt.4245
• Super-Mendelian inheritance mediated by CRISPR–Cas9 in the female mouse germline.  Grunwald et al,  7 February 2019 | VOL 566 | Nature | 105; Controversial CRISPR ‘gene drives’ tested in mammals for the first time. Nature News 06 July 2018; A ‘gene drive’ makes its debut in mammals Science 13 Jul 2018: Vol. 361, Issue 6398, pp. 118

The Genome Project-Write
The Genome Project-Write started a few years ago. Its primary goal of Genome Project-write is to reduce the costs of engineering and testing large (0.1 to 100 billion bp) genomes in cell lines by more than 1,000-fold within 10 years. GP-write will include whole genome engineering of human cell lines and other organisms of agricultural and public health significance.
• Center of excellence for engineering biology: https://engineeringbiologycenter.org/



Best regards
Marie
posted on 2019-03-06 08:38 UTC by Ms. Marie Nyman, The Swedish Gene Technology Advisory Board
RE: Some synbio papers [#9368]
Many thanks, Marie, most useful!

Marie has provided an overview not only of the technologies but also their applications (at a high level) in her intervention. As a regulator, I note that while being aware of and up to date with new techniques & technologies (and their capabilities/potentials) is useful, the critical issue remains the final product and the proposed application (including receiving environment). Ultimately there are different ways (tools/techniques) to reach the same final product (and applications will continually grow/expand, limited only by human ingenuity), so the technology itself is of less importance than its application, and the means to manage that application.

Marie also raises the important point that the definition of synthetic biology remains problematic. In the discussion on point 5 of this forum I will again raise the point that we need a better definition, perhaps linked to whether 'substantial equivalence' can be considered to apply.

Regards
Ben (with greetings from South Africa)
posted on 2019-03-06 10:31 UTC by Mr. Ben David Durham, South Africa
RE: Some synbio papers [#9369]
Hello again
Just a few weeks ago the first genome edited crop was released. It was a high oleic acid soybean developed by the company Calyxt. I do not regard it as a product of synthetic biology, but since several countries, including the US, will not regulate genome edited crops if there are no new DNA integrated I think we will see a lot of different crops breed with genome editing tools on the market quite soon.

PS. Cibus rapeseed developed through their Rapid Trait Development System has been on the market for a few years and that technique can also be regarded as genome editing, although there are no "scissors" involved.

Marie
posted on 2019-03-06 10:54 UTC by Ms. Marie Nyman, The Swedish Gene Technology Advisory Board
RE: Some synbio papers [#9370]
Hello,

I would like to congratulate the moderators Maria and Casper for their willingness to chair the on-line forum on SynBio.
My name is Angela Lozan, I am representing the Moldovan Ministry of Agriculture, Regional Development and Environment, Biodiversity office.
Thanks to Marie and Ben for their interventions and information on the latest publications on synbio.

I would also recommend a number of published articles with the latest research developments in the field, published by prestigeous scientific editorials as Natura, Springer, Molecular biotechnology, Cell biotechnology etc.:
https://www.vesti.ru/theme.html?tid=107945
https://www.omicsonline.org/scholarly/synthetic-biology-journals-articles-ppts-list.php
http://discovermagazine.com/tags?tag=synthetic+biology
http://news.mit.edu/topic/synthetic-biology
https://academic.oup.com/synbio/search-results?page=1&allJournals=1&f_ArticleTypeDisplayName=News&fl_SiteID=5419
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3037580/
https://axial.acs.org/2019/01/02/read-the-top-trending-2018-articles-from-acs-synthetic-biology/
https://bmcmolbiol.biomedcentral.com/articles
https://www.springer.com/la/book/9781493977949
https://www.nature.com/articles/s41568-019-0121-0
https://www.nature.com/articles/s41586-019-0978-9
https://www.the-scientist.com/news-opinion/synthetic-bacteria-help-treat-phenylketonuria-in-mice-64656
https://www.the-scientist.com/modus-operandi/synthetic-stem-cells-regenerate-heart-tissue-in-mice-31426
https://www.the-scientist.com/news-opinion/improved-semisynthetic-organism-created-32162
https://academic.oup.com/synbio/article/4/1/ysz006/5304378
https://www.cell.com/trends/biotechnology/fulltext/S0167-7799(15)00274-7

Angela
MD
posted on 2019-03-06 11:33 UTC by Ms. Angela Lozan, Republic of Moldova
RE: Some synbio papers [#9372]
I hope to have the opportunity later in the discussion to formulate a more complete response to the topic, but I wanted to just interject here to point out that it is not correct to say that the U.S. and several other countries will "not regulate" gene edited crops.  Some countries have determined that these crops don't fall under regulations covering LMOs (GMOs, transgenics, or other nearly synonymous terms depending on the regulatory system in questions).  But this should not be confused with being wholly unregulated.  There are many different applicable regulations that might apply to a crop plant that have nothing to do with it being an LMO. 

I'm sure representatives of these countries will provide their own responses as they see fit, but I think this is an important point of clarification that we should keep in mind during the discussion.

I also have to point out that, while I completely support the sharing of information around developments in gene editing and gene edited crops, I am very concerned that "synthetic biology" is becoming a catch-all phrase for any and all developments in crop breeding - whether or not these developments require any special consideration under the Cartagena Protocol.  I see that Marie prefaced her original post by highlighting the difficulty in determining what is being considered "synthetic biology," which is very understandable.  I agree wholeheartedly with Ben (post #9368) that a more meaningful and clear definition is needed.  Right now, we are operating with a variety of unstated definitions and it will be very difficult to have meaningful dialogue without a shared understanding of what is meant by "synthetic biology."
posted on 2019-03-06 12:22 UTC by Mr. Andrew Roberts, International Life Sciences Institute Research Foundation
RE: Some synbio papers [#9374]
Thanks for the clarification. I see now that I missed out to write GMO in connection with not regulated.
Marie
posted on 2019-03-06 14:06 UTC by Ms. Marie Nyman, The Swedish Gene Technology Advisory Board
RE: Some synbio papers [#9378]
I am Jeremy Sweet an Environmental Consultant in UK. I send greetings to all and I thank you for allowing me to contribute to this Forum. In response to Andrew Roberts and others I agree we need a clear definition and agreement on what is synthetic biology . The one I use is from the Royal Society : "Synthetic biology is an emerging area of research that can broadly be described as the design and construction of novel artificial biological pathways, organisms or devices, or the redesign of existing natural biological systems."
It is the second part of the definition that is problematic as one could argue that gene editing and transgenics also redesign biota, and so when do these techniques become Synthetic Biology ? Is it when the scale of change to an existing biological system goes beyond what is normally achieved by transgenics and gene editing ?  I think it would be very useful to get agreement on this otherwise the Forum will be supply numerous references to techniques which are not within the scope of this study.
posted on 2019-03-06 17:24 UTC by Mr. Jeremy Sweet, JT Environmrntal Consultants Ltd
RE: Some synbio papers [#9434]
Hello again colleagues.

Jeremy Sweet raises interesting questions in his intervention #9378. To some degree these questions are derivative of the chosen definition, but they are nevertheless on the minds of many. My focus is on the word 'systems' and at what scale engineering of systems may be captured in our discussions.

With the rapid pace of development and intended commercialisation of "open air" applications of the reagents of synthetic biology techniques (please see, eg, my post #9431) is the means to redesign existing natural or agricultural landscapes at the ecosystem scale. Even if each individual change is brought about by what one would consider to be not synthetic biology (for some, that might mean a gene edit), the combination of changes and the variety of species simultaneously modified is beyond what anyone I know now calls "transgenesis" as we have seen in commercialised products since the 1990s.

While this might appear to be hypothetical, within the forum is discussion of gene drives for multiple purposes and could include multiple different drives operating coordinately in the same ecosystem. In addition, mass delivery technologies are being claimed in the patent literature.

For example, in the patent “Methods and compositions for introducing nucleic acids into plants” is described a method to in situ deliver nucleic acids to plants at the field scale, presumably using tools such as tractor mounted sprayers or airplanes. Along with my post 9431, it is easy to anticipate both protein and nucleic acid packages being deployed at ecosystem scales.

Best wishes
Jack
posted on 2019-03-08 23:57 UTC by Mr. Jack Heinemann, University of Canterbury
RE: Some synbio papers [#9373]
Hello all,

One new and powerful synthetic biology technology/tool that has far reaching implications and potentially innumerable applications that the forum should be aware of is that genetic codes based on eight nucleotides vs four has now been developed. This essentially doubles the coding power of DNA:

"By combining four synthetic nucleotides with the four found naturally in nucleic acids, researchers have created eight-letter DNA molecules that look and behave like the real thing, and are even able to be transcribed into RNAs, according to a paper in Science today (February 21). With twice the information storage capacity of natural nucleic acids, these eight-letter, or “hachimoji” molecules—could have countless biotechnological applications, say scientists."

"Hachimoji DNA could even be combined with other types of artificial nucleotides that are based on a different base-pairing chemistry, thus potentially increasing functionality yet further, says Ichiro Hirao of the Institute of Biotechnology and Nanotechnology in Singapore who was not involved with the research."

S. Hoshika et al., “Hachimoji DNA and RNA: A genetic system with eight building blocks,” Science, 363:884–87, 2019. (https://www.the-scientist.com/news-opinion/dnas-coding-power-doubled-65499)

Kind regards,

Bruce Dannenberg
Founder and CEO, Phytonix Corporation
posted on 2019-03-06 12:48 UTC by Mr. Bruce Dannenberg, Phytonix Corporation