Invention of DNA "Page Numbers" Opens Up Possibilities for the Bioeconomy
caltech.edu65 points by dagurp 4 hours ago
65 points by dagurp 4 hours ago
That page numbers in books were only invented 50 years after the printing press is a fun snippet from the article
Many times obvious things are only obvious once you see them. Like roller suitcases.
Chemical modifications of DNA are so amazing, and underpin so much DNA related research and engineering. Illumina and Moderna would not exist without DNA mods. It’s very cool that the set of tools is expanding further!
“ Guided by the removable DNA page numbers, Sidewinder achieves an incredibly high fidelity in DNA construction with a measured misconnection rate of just one in one million, a four to five magnitude improvement over all prior techniques whose misconnection rates range from 1-in-10 to 1-in-30.”
I wonder if this is even a problem, since you could amplify the correct sequence with PCR afterward.
pcr amplifies all sequences, correct or wrong, no? and as I understand it, it works on short snippets the best.
It amplifies sequences that contain the two primer sequences on each end of the target. So if you had synthesized sequence XYZ with some mistakes like YZX, then you could target X and Z and purify.
You're correct that PCR has a limited max length, but it is longer and cheaper than vanilla DNA synthesis.
Ok that’s it for me. Selective breeding via BLUP at least had a speed limit, this is going to end with cronenburg brundlefly creations.
Movies that come to mind that involve genetic building at this level are Gremlins 2, The Clone Wars, and some in the Alien franchise.
Yes, someone has attempted in the last to breed or alter for specific traits, we’ve cloned many kinds of life, and if there was extraterrestrial life here, someone probably mixed it with humans and animals.
But the pace of this is not going to increase anytime soon, if history is a judge. CRISPR was scaring people years ago when publicized, but those worries were unfounded and so shall these be. Life is much harder than coding apps.
Saw the headline and thought we were coming full circle on GEB -- a discovery of page number mechanisms in DNA functioning like GOTOs in code.
It's instead a way to stitch together longer sequences of DNA. Still very cool
Such a simple concept took this long to discover? Now we just need a way of packing the DNA strings into blank cells reliably.
Cool. I wonder how long until we are able to steal anti-cancer genes from whales.
The article mentions AI multiple times even though the invention appears to have nothing to do with AI. I guess it’s important to have it as a marketing buzzword.
Sidewinder itself sounds neat.
Has anyone dabbled in hobbyist genome editing and DNA synthesis or is this something that requires a huge pile of capital?
Probably AI in the sense of what Google DeepMind has been up to with the protein folding and other biological simulations, instead of the LLM variant of AI.
This is probably the only way "humans" are going to colonize any planets other than Earth. And probably lots of new places on Earth too.
Just include the genes for extreme-cold or extreme-arid climates. Or the genes for low oxygen environments, or even for metabolizing useful things from eating rocks. Or from spending 24 hours a day in salt water.
The ease of this "just" is the most concerning thing in the context of humankind's survival.
There is no way it is just "just". And we should start from simpler stuff like vitamin B12, C and D.
Everything is “just” eventually.
Just tell your car to drive you to the airport. On the way just tell it to play that song you like.
Alas, one's happiness (as in genuine inner wellbeing, as opposed to the consumption-based external one) is no "just" matter, and never will be.
Imagine if we could turn our bodies into perfect spheres, and then adjust genetic beauty preferences to match it.
Oh if only science was not constrained by ethics.
I can already see the people protesting against the creation of space marines.
Science has never been constrained by ethics.
The same scientists who cry about ethics, have happily experimented on mice and guinea pigs in their labs, even if it causes the deaths or distress of those little sentient beings.
Mutations/mutatives like Halo's Master Chief and Marvel's Super Soldier serum won't remain sci-fi for much longer, methinks.
And save human life at the same time? Experiments are not just about torturing animals; people spend a lot of time optimizing for experiment design.
Human life is meaningless to people without ethics. For them, humans are guinea pigs; or worse - slaves.
Talking of "human life" and "experiment", did you know about this billionaire chap and what he's been really doing in the name of science, experiment and charity? https://m.economictimes.com/industry/healthcare/biotech/heal...
The text details the methodology for "Sidewinder," a DNA assembly approach that utilizes oligo-derived heteroduplex fragments, barcode sequences, and toehold-mediated ligation. The process relies on computational design (NUPACK), specific thermal cycling protocols, and rigorous sequencing validation to assemble and screen complex DNA constructs.
Fragment and Barcode Design
Sidewinder fragments are composed of DNA oligos. The design process relies on calculating the length of a construct and a barcode to determine the maximum bases of coding information.
Toeholds: Standardized to 10 bases. Ligation is effective at ≥±6 bases from the Sidewinder helix; 10 bases allow sufficient distance for ligase docking.
Barcodes: Designed to be compatible with toeholds using a "guess-check" method or NUPACK Python scripts. Barcodes are screened for secondary structure and crosstalk at 50°C.
Ligase Selection: Taq ligase and HiFi Taq ligase were selected for their stability at high temperatures and efficiency at the 3-way junction (3WJ).
Oligo Preparation and Annealing
Sourcing: Oligos were synthesized by Millipore-Sigma. Standard desalt purification was generally sufficient, though PAGE purification was used for specific characterization steps.
Heteroduplex Formation: Coding oligos (phosphorylated via T4PNK) and barcode oligos are annealed in a PCR tube. The mixture is heated to 98°C and ramped down to 25°C to form stable heteroduplexes.
Purification: Annealed heteroduplexes are purified via PAGE gel extraction.
Assembly Protocols
The authors describe two primary assembly conditions using HiFi Taq ligase with fragments at equimolar concentrations (~1 nM):
Cycling Protocol: Cycles between 85°C (1 min) and 50°C (2 min) for 100 cycles, followed by a 1-hour hold at 50°C.
Ramp Protocol (e.g., h-fibroin): Heats to 85°C, slowly cools to 50°C, and incubates overnight at 50°C.
These methods were benchmarked against conventional 2-way junction (2WJ) and Gibson assembly methods.
What's the source of the text? It seems to be either a copypasta from a journal article or LLM-generated (and not your own text).
LLM–generated summary. A human summary wouldn't specify the temperature used because it's irrelevant.