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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
by koeng 3y ago
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
- logtempo 3y agohttps://genomebiology.biomedcentral.com/articles/10.1186/gb-2004-5-8-r58 https://genomebiology.biomedcentral.com/articles/10.1186/gb-... Might interest you!
- koeng 3y agoThat'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
- jmkni 3y agoHow 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)
- stavros 3y agoVery very small tweezers.
- fuzztester 3y agoWith nanotechnology.
- hackable_sand 3y agoAfter 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...
- yakorevivan 3y ago[dead]
- koeng 3y agoI 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-expression-and-regulation/biotechnology/a/overview-dna-cloning 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!
- javcasas 3y agoThat is some seriously cool stuff.
- reaperman 3y agoThank you so much for posting this. It's wonderful to hear how excited you are about it all.
- JohnMakin 3y agothis is the coolest thing I have ever read. How did you even get into that?
- koeng 3y agoI 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-editing-virus.html https://www.nytimes.com/2018/05/14/science/biohackers-gene-e...
- minzi 3y agoIncredible! Obviously tons of credit to you individually, but also huge kudos to your teacher for encouraging your curiosity.
- owenpalmer 3y agoThat's so cool! If I may ask, what is your level of education?
- koeng 3y agoI 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.
- JohnMakin 3y agozot zot
- tanseydavid 3y agoI swear I feel like I'm dreaming this thread.
- kuczmama 3y agoThat is very cool. I'm curious if you can share some of the things people are using this synthetic DNA for?
- koeng 3y agoI 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
- unsupp0rted 3y agoI 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.
- samstave 3y agoIs he a vendor in my Fallout 4 gameplay?
- koeng 3y agoA 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.
- unsupp0rted 3y agoHe 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.
- blueferret 3y agoNow 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...?
- xyst 3y agoSynthetic 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.
- koeng 3y agoThe 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://keonigandall.com/posts/sporenet.html
- KRAKRISMOTT 3y agoDo you have in-house protocols or are you using the off the shelf stuff?
- koeng 3y agoI 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
- b20000 3y agoare you not scared of synthesizing deadly bacteria?
- koeng 3y agoNo, I know pretty much everything I synthesize. Once I don't, I'll just connect some screening software.
- b20000 3y agowhat if the software misses something?
- koeng 3y agocan you give a specific instance of a sequence that would be dangerous in a cloning strain and not screenable?
- deleted 3y ago[deleted]
- datascienced 3y agoYou are asking for a counterexample but I think s/he was asking for what assurances the software can provide. Is it proven to be perfect, bug free in both specification and the physical analysis? Remember compared to you assume we are all laymen. It would be interesting for us on the armchairs how such software even works. Is it like (ahem!) antivirus software looking for patterns?
- koeng 3y agoThe reasons I ask for a counter example is because the number of “what ifs” are pretty much unlimited and easy to come up with, whereas I have to do a lot more thinking to answer them. It’s asymmetric and gets tiring Answer is: no, not proven to be perfect. Most source is closed for the software. There is no specification. Never been a red team trying to break it. Unknown if it’s ever stopped any threats. There is no requirement to do it, and it’s all voluntary (though pretty much all synthesis providers do it). Mostly they just hash kmers and translations thereof and scan a pathogens/functional database. So implementable in a simple KV store for the most part. The bigger problem is false positives, and most work is done in de-shittifying the upstream pathogens data. Here’s a good paper: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9988571/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9988571/ Last I checked all the groups charged a lot of money for access, unfortunately, and I’m not really big enough to join a group like the International Gene Synthesis Consortium :(
- drones 3y agoIf I ever met you in real life I think you would be the coolest person I've ever met.
- koeng 3y agoThanks!