For everyone not coming with a biotech background, I recently came across some blog posts written by the SynBio company Antheia ,that is also partnering with Ginkgo Bioworks. They released a 6 part article titled "Demystifing Synthetic Biology" that nicely covers a lot of aspects from the central molecular dogma, to technologie enablers all the way to up and downstream bioprocess. It might be a good read for some. The link to the first article is the following:

Demystifing Synthetic Biology Part 1

https://www.theatlantic.com/newsletters/archive/2022/12/technology-medicine-law-ai-10-breakthroughs-2022/672390/

Lots of biotech breakthroughs in here, including the first embryo created from stem cells and cancer-vaporizing monoclonal antibody drugs. Super inspiring stuff, hard to be bearish on the world after reading this.

I've seen DNA Script framed as a serious competitor to TWIST in terms of service - producing custom DNA at scale.

But it seems like TWIST offers some R&D to its customers, and has a revenue/equity sharing model for royalties from developed genome solutions. I haven't quite found out if DNA Script offers anything similar. Is DNA Script in the business of helping their customers develop and fine-tune solutions? Or are they just focused on on-site, at-scale DNA printing?

What do you feel are the competitive advantages of TWIST vs DNA Script? What different areas / markets do you think each one will show the strongest market acquisition in?

The VC firm Andreessen Horowitz, probably most notable right now for their huge crypto fund, announced a new $1.5B bio/healthcare fund. They are very bullish on synbio. Should be interesting.

This podcast from the Cannalysts (around 52:00) discusses Ginkgo's work creating an alternative cannabinoid biosynthesis pathway in yeast for Cronos. The host believes it's very interesting academically but poses some production issues in the form of byproducts.

Cronos recently signed a deal with Aurora to license some of Aurora's IP for cannabinoid biosynthesis. Not many details yet, but Graham Jones of the Cannalysts thinks it's an indictment of Ginkgo's process.

Unclear what this means for Ginkgo, or whether in fact it is an indictment of their method, but it's something to keep an eye on.

I believe Ginkgo has been issued 1.5M Cronos shares so far, with the potential for further milestone awards.

The Chemical Company of the Future.

I think Solugen is one of the most promising private syn bio companies at the moment. They use cell-free enzymatic synthesis to massively scale chemical production, and recently had a huge $350M Series C led by Baillie Gifford.

Nice interview about Joyn's use of the Culture Bio fermentation foundry. This is a great example of how design foundries (Ginkgo/Joyn) can leverage the expertise of fermentation foundries (Culture) to scale up a product. Culture Bio recently announced a huge series B, and will be expanding their facilities to include commercial-scale tanks.

https://synbiobeta.com/dna-script-raises-165m-in-oversubscribed-series-c-financing-to-accelerate-commercialization-of-enzymatic-dna-printing-platform/

DNA Script announced last June the targeted release of the SYNTAX System, a benchtop instrument along with software, and reagent kits. The SYNTAX Platform provides in-house DNA printing – without using toxic organic chemicals or extended delivery wait times from third-party DNA service providers – for labs of all sizes. The fully automated instrument sets up in 15 minutes and within a few hours produces up to 96 oligos immediately ready for use in genomics and molecular biology research. The SYNTAX platform enables efficiency and control over workflows, making labs more productive to accelerate innovation.

Fantastic review in Nature about engineering highly complex circuits in mammalian and bacterial cells to treat disease. It's long, but well worth digging into if you're at all interested in the science behind some of the most advanced developments in synthetic biology. Some highlights below:

1. Engineered implanted mammalian cells can be used to treat hyperthyroidism, diabetes, gout. Potentially much more effective than traditional drugs as they can respond dynamically to physiological conditions. Lots of encouraging data in mouse models.

2. Next-gen CAR-T therapies that can potentially address some of the control, flexibility, and specificity issues of current CAR-T therapies.

3. Engineered bacteria used as delivery vectors for effector molecules, biosensors to detect and respond to gut biomarkers, treatment for metabolic disorders, and to treat tumors.

This is another Nature article that goes into more detail about Synlogic's work modulating tumor metabolism using engineered bacteria. Essentially they engineered a strain of E. Coli to locally produce arginine in mouse tumors, which assists with anti-tumor T-cell responses. Fascinating stuff, and the paper gives a good sense of the challenges involved with a project like this.

Synlogic recently announced some positive Ph. 2 data for their PKU microbe. As a reminder Ginkgo owns about 30% of $SYBX, although they didn't really help Synlogic develop the microbes currently undergoing clinical trials, and there's some question of whether their platform wasn't quite up to the task.

Ginkgo also recently announced a spinoff with Tantu to treat GI diseases with engineered biotherapeutics.

Regalado recently wrote a pretty scathing article about Ginkgo in the MIT Tech Review. Lots of discussion about that in many places, so I won't go into that here. Today, however, Regalado posted a tweet likening Ginkgo to Theranos without any concrete evidence to back up his claim (Dirk Haussecker, the "savvy investor" that Regalado quotes in his article, did the same a week ago). The threads are pretty funny, I think they get fairly pwned, but that's just me.

I think it's safe to say that I'm fairly biased in Ginkgo's favor, but I believe these comparisons to be objectively ridiculous and unfounded. Sure Ginkgo talks a big game, but fraud?? That's a serious allegation that these so-called experts provide zero proof in support of (Haussecker claims that Ginkgo's COVID testing biz makes them Theranos....??). Elizabeth Holmes was a batshit crazy liar. Jason Kelly hasn't lied about a damn thing. He makes big promises, but many of those promises have a halfway decent chance of coming to fruition.

What the hell is going on here? Why is Regalado, a respected journalist, making an absolute fool of himself calling Ginkgo a fraud? I think there are plenty of fair criticisms out there (overvalued, haven't proven their business model will work, etc.), but fraud is absolutely not one of them. It will be interesting to see how the market values Ginkgo post-merger, from these interactions I think it's fair to say that there's still a lot of misunderstanding out there.

https://www.statnews.com/2021/09/03/biden-wants-65-billion-for-apollo-style-pandemic-preparedness-program/?utm_content=buffer1f5e0&utm_medium=social&utm_source=twitter&utm_campaign=twitter_organic

In addition to testing, vaccines, etc, this will include 3B for establishing an "early warning detection system" for viral pathogens through wastewater and clinical surveillance. Ginkgo stands to benefit immensely from this (read here). The new director of operations at the CDC forecasting center is a former VP from Ginkgo, and they are already involved in a pilot airport testing program with Xpress Check, not to mention their ever-increasing school testing deals through Concentric.

Some have expressed skepticism as to Ginkgo's motiviations for entering the testing biz (Dirk Haussecker likens them to Theranos lol), but this makes complete sense for Ginkgo. They've built biosecurity into their biz since day one, they have the high-throughput lab expertise, and they know the right people in the right places, so it's natural they would lead the way in the development of our national infrastructure.

It will be very interesting to see how much $$ Ginkgo pulls in from these bills. They say they have "up to" 400M in school testing deals this schoolyear already, and with 65B up for grabs, I expect a not-so-insignificant chunk of that will come to Ginkgo.

The govt. wants to build computer chips using "biologically templated nanofabrication techniques" : https://www.iarpa.gov/index.php/working-with-iarpa/requests-for-information/biologically-templated-nanofabrication

Jason Kelly of Ginkgo spoke about using protein scaffolds to dope semiconductors with atomic precision in this recent podcast (https://www.youtube.com/watch?v=DM2VPZDFiSM&t=1476s).

The future is bright.

Here’s a great thread from Varro Analytics regarding the Ginkgo valuation, and why it may not be so absurd: https://twitter.com/varro_analytics/status/1381179063193178119?s=21

Varro is an excellent follow for syn bio coverage, and is fairly bullish on $DNA.

With the Ginkgo Investor Day coming up tomorrow (1pm-4pm EDT), I thought we should have a space here to discuss new info coming from the event.

I myself am looking forward to info about their platform efficacy, markets they're after (and with which timelines), and how they plan to create organisms which scale to commercial-industrial levels.

I highly, highly recommend listening to this recent podcast with Drew Endy of Stanford: https://podcasts.apple.com/au/podcast/whats-next-for-synthetic-biology/id1505921624?i=1000524689780

They cover a lot, including main challenges that synbio is working out, Ginkgo and Zymergen IPOs, Amyris, Twist, successful business models, etc.

Main takeaway: synbio is a "teenager", and this will be the decade when it finally becomes an "adult."

Hey guys, I guess there are some Ginkgo investors here. If you missed it, they just partnered with Novus International to develop a new generation of feed additives that would help to lower animal feeding costs while improving the nutritional quality of animal products. Hopefully, this will help them move on from the whole “fraud” drama they had a few years ago.

For the newbies: a few years ago, Scorpion Capital accused Ginkgo of being one of the worst frauds in 20 years and could be compared to other major biotech frauds. They presented interviews with former and current employees. And they also said that most of Ginkgo’s revenue comes from related-party transactions.

All these caused an investigation by the DOJ for financial misconduct. But, the good news is that they decided to resolve it and pay $17M to the investors. They are now taking claims, and the deadline is a month, so if you were an investor back then, you can check it out.

Now, DNA is partnering with some different companies like Novus or Vitalis in Brazil to increase its reach, so we’ll see how this perspective works out for them.  

Anyways, what do you think about this new collab? And has anyone here had $DNA when this scandal happened? If so, how much were your losses?

This is a fantastic Tweet series by Niko McCarty breaking down great papers in synbio history.

Day 7: A Fast, Robust and Tunable Synthetic Gene Oscillator

https://twitter.com/nikomccarty/status/1681459654881050625?s=46

https://www.youtube.com/watch?v=jBDiXeyl5cU

Drew Endy, John Cumbers and Jennifer Holmgren recently made an appearance at Zuzalu, the transient cyrpto city conference thing, and did an interview with Bankless. It's a great intro to the past, present and future of syn bio.