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Invention of DNA "Page Numbers" Opens Up Possibilities for the Bioeconomy

https://www.caltech.edu/about/news/invention-dna-page-numbers-synthesis-kaihang-wang
33•dagurp•2h ago

Comments

smackeyacky•1h ago
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.
unsupp0rted•1h ago
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.

wartywhoa23•1h ago
The ease of this "just" is the most concerning thing in the context of humankind's survival.
vee-kay•34m ago
Then I recommend you don't find out what "Project Molecule" intends to do.
Traubenfuchs•1h ago
Oh if only science was not constrained by ethics.

I can already see the people protesting against the creation of space marines.

whycome•37m ago
No laws on mars
vee-kay•31m ago
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.

melagonster•15m ago
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.
vee-kay•35m ago
Is there a gene to avoid getting addicted to doomscrolling? ;-)
krzat•29m ago
Imagine if we could turn our bodies into perfect spheres, and then adjust genetic beauty preferences to match it.
throwaway198846•24m ago
There is no way it is just "just". And we should start from simpler stuff like vitamin B12, C and D.
unsupp0rted•19m ago
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.

jryb•1h ago
Paper: https://www.nature.com/articles/s41586-025-10006-0
krzat•34m ago
Cool. I wonder how long until we are able to steal anti-cancer genes from whales.
trebligdivad•24m ago
That page numbers in books were only invented 50 years after the printing press is a fun snippet from the article
nullbyte808•16m ago
Such a simple concept took this long to discover? Now we just need a way of packing the DNA strings into blank cells reliably.
jycnaw•10m ago
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.

nullbyte808•4m ago
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.

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Invention of DNA "Page Numbers" Opens Up Possibilities for the Bioeconomy

https://www.caltech.edu/about/news/invention-dna-page-numbers-synthesis-kaihang-wang
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