I’ve been working on a synthetic DNA assembly company. Basically, I figured out how to assemble DNA for people at a fraction of what it normally costs, so they give me a sequence, and then I make it in real life for them, then ship it to them.
Most of my customers have been AI protein designers, ironically. Turns out SOMEBODY has to wrangle atoms in the real biological world and that’s me!
After almost a year of work I finally smoothed out all the kinks in the process, so can now go from a design to synthetic DNA in a cell in about a week (not counting oligo pool synthesis time). I can do about 600,000bp per week, which is large enough to synthesize the smallest bacterial genome (each week), tho I only do about 1000bp fragments. I’m also completely bootstrapped and self funded, and only get help from my several opentrons robots
this is the coolest thing I have ever read. How did you even get into that?
I found a virology textbook at the local Catholic book fair when I was in 6th grade, got hooked, teacher in 7th grade let me order GFP transformation kits to the school that I could do at home, then off to the races from there. I was in this article if you're interested in more deets: https://www.nytimes.com/2018/05/14/science/biohackers-gene-e...
That's so cool! If I may ask, what is your level of education?
I never went to university or anything, but did work for 4 years at UCI in directed evolution / mitochondrial engineering, then 3 years at Stanford on the FreeGenes project (got invited to work at both). Barely passed high school cause I didn't care about my classes there.
zot zot
Cool! Though it's a bit scary how easy it would be for someone to make something dangerous as mentioned in the nyt article. The 2018 article ends:
I guess we may have seen that kind of thing happen a year later with covid though that would have been government sponsored mucking around rather than DIY if it wasn't natural. Not sure how we stop that happening again?
Personally, I think the threat from the biologics itself is a little overstated. If COVID was released from a lab (I think it was natural), it was most likely due to bad governance and management of the lab. For DIY things - most DNA can be screened. I have had companies offer screening services for about 50k-100k a year. I can't afford that! So hopefully a free service or something near to that comes online.
That's awesome. I also got hit hard by the science bug (pun intended) as a kid, which I can partly attribute to finding a random virology textbook in an academic bookstore dollar bin. I was obsessed with virology at least until college. I ended up majoring in math in college but made it through Ochem II and did some lab internships before committing to that path. Now I'm a ML/software engineer with a healthy interest in biochem.
I swear I feel like I'm dreaming this thread.
Incredible! Obviously tons of credit to you individually, but also huge kudos to your teacher for encouraging your curiosity.
I once met a freelance bespoke industrial adhesive maker. He takes orders from various factories for adhesives with specific properties, then uses his knowledge of chemistry + trial & error to make one that fits the specs provided.
Bespoke synthetic DNA is much cooler though.
A bespoke freelance industrial adhesive maker sounds like such a niche job, that's awesome. I would love to see a hackernews-type post with details of how he thinks about making a specific adhesive.
He was a Russian guy, normally living in Russia. HN post is unlikely, but I would love to see folks of this sort post here.
We both happened to be traveling in the same country one New Year's and got to talking.
Is he a vendor in my Fallout 4 gameplay?
How the fuck does one "assemble DNA" lol
Sorry but that's so outside of my understanding it reads like pure science fiction
(I'm sure it's a thing, I'm just a moron)
Very very small tweezers.
After we did DNA extraction in high school we were provided toothpicks to serve the strands onto a microscope plate.
So yeah, at a certain mass...
I use restriction enzymes + ligase to cut DNA, then paste it back together at specific sequences. It's pretty simple honestly! https://www.khanacademy.org/science/ap-biology/gene-expressi...
The key is doing that at an industrial scale, reproducibly, with hundreds to thousands of plasmids at once. Becomes less simple. You encounter bullshit problems with biology, which I guess is valuable because it makes a moat!
are you not scared of synthesizing deadly bacteria?
No, I know pretty much everything I synthesize. Once I don't, I'll just connect some screening software.
what if the software misses something?
can you give a specific instance of a sequence that would be dangerous in a cloning strain and not screenable?
Now this is interesting. I've read about using synthetic DNA for data storage, but other uses surely abound.
I don't suppose you'll need documentation help at some point in the near future...?
Synthetic DNA for data storage seems much higher to degradation (ie, heat, light, or other sources of radiation). Not sure if I would use syn DNA to for anything long term.
The oldest sequenced DNA is 1.6 million years old. In the right conditions, it lasts far longer than pretty much any storage method right now. Plus I also sometimes store things in Bacillus subtilis, which is very hardy https://keonigandall.com/posts/sporenet.html
https://genomebiology.biomedcentral.com/articles/10.1186/gb-...
Might interest you!
That's how Twist/Agilent do oligo pool synthesis (and Dynegene now). I'm pretty interested in the Genscript / Avery digital method of electrochemical synthesis. Turns out those pools ain't good enough to be used in a biological context, which is where I come in - I can assemble them well into sequence perfect stuff
That is very cool. I'm curious if you can share some of the things people are using this synthetic DNA for?
I can share a few things! (but definitely not all)
- One is finding different T7 RNA polymerases with unique properties by manipulating the backbone. They can be used for things like in-vitro RNA production for vaccines - Another is synthesizing a phage that has been sequenced for a specific organism, but that the samples are now lost of. So resynthesizing that genome from scratch - A different project (personal one) is building a DNA parts toolkit with standardized DNA parts so you can combine em together like legos. Pretty much nowhere but FreeGenes has open source genetic parts (I used to run that project), and I think open source genetic parts need to be in the world
If I ever met you in real life I think you would be the coolest person I've ever met.
Thanks!
Do you have in-house protocols or are you using the off the shelf stuff?
I sometimes derive protocols from off-shelf ones, but pretty much everything beyond that is in-house. Most off-shelf protocols work for 1 sample in 1 tube - I had to adapt them to working on 1 plate of 384 tubes (and get those to work with robots). There is a significant amount of robotic code that I use, and a few custom protocols that are from a random obscure scientific paper in 1980s or 1990s
Thank you so much for posting this. It's wonderful to hear how excited you are about it all.
That is some seriously cool stuff.