[HN Gopher] Invention of DNA "page numbers" opens up possibiliti...
___________________________________________________________________
Invention of DNA "page numbers" opens up possibilities for the
bioeconomy
Author : dagurp
Score : 134 points
Date : 2026-02-06 10:26 UTC (12 hours ago)
(HTM) web link (www.caltech.edu)
(TXT) w3m dump (www.caltech.edu)
| smackeyacky wrote:
| 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 wrote:
| 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 wrote:
| The ease of this "just" is the most concerning thing in the
| context of humankind's survival.
| vee-kay wrote:
| Then I recommend you don't find out what "Project Molecule"
| intends to do.
| imzadi wrote:
| Care to enlighten? Google has nothing meaningful.
| vee-kay wrote:
| "Project Molecule": a proposed megafund in collision with
| Epstein, seeded with Gates-foundation capital and
| JPMorgan clients, with a sinister purpose : controlled
| pandemics!
|
| Buried in the Epstein files is a 14-page JPMorgan
| proposal called Project Molecule--a formal partnership
| with the Bill & Melinda Gates Foundation to transform
| pandemic preparedness into a permanently governed,
| privately controlled, transnational system of vaccine
| procurement, surveillance, and global health finance--
| developed within the same institutional ecosystem in
| which the convicted sex offender (Epstein) operated as a
| connective broker between Wall Street, global health, and
| political power.
|
| https://www.nytimes.com/2025/09/08/magazine/jeffrey-
| epstein-...
|
| https://portside.org/2025-09-15/how-jpmorgan-enabled-
| crimes-...
|
| https://www.tumlook.com/katiepavlich/post/807627515385561
| 088
|
| https://www.moneycontrol.com/world/how-jpmorgan-enabled-
| jeff...
| vee-kay wrote:
| LOL, I knew this would be downvoted.
| vee-kay wrote:
| *collusion
| 9dev wrote:
| These files are a never ending quell of evilness. It's
| really fascinating. One day people are going to realise
| the upper 1% are just that--very few....
| vee-kay wrote:
| And those 1% elites are very rich and very powerful.. so
| they can do whatever they want.. (and that includes
| funding and controllimng unethical scientific
| experiments)..
|
| World's top 1% own more wealth than 95% of humanity, as
| "the shadow of global oligarchy hangs over UN General
| Assembly," says Oxfam: https://www.oxfam.org/en/press-
| releases/worlds-top-1-own-mor...
|
| World's richest 10 percent holds more than three quarters
| of the world's total wealth:
| https://www.statista.com/statistics/1417996/wealth-held-
| rich...
|
| Ten richest men double their fortunes in pandemic while
| incomes of 99 percent of humanity fall:
| https://www.oxfam.org/en/press-releases/ten-richest-men-
| doub...
|
| Over the past 30 years the U.S.'s top 1% got richer, and
| now hold nearly a third of the nation's wealth:
| https://fortune.com/2024/10/08/congressional-budget-
| office-w...
| mmooss wrote:
| For the most part, they only have the power others give
| them.
| wartywhoa23 wrote:
| Thanks for the heads-up!
| Windchaser wrote:
| >The ease of this "just" is the most concerning thing in the
| context of humankind's survival.
|
| Right? I wouldn't expect genes for heat/cold tolerance in
| other organisms to necessarily be useful in humans. They work
| by mechanisms that are useful for that organism, but humans
| have our own set of problems.
|
| It's like saying you can strap a jet engine on to a tractor
| and expect farm work to massively speed up. No: the machinery
| doesn't translate for a clean swap like that.
| Traubenfuchs wrote:
| Oh if only science was not constrained by ethics.
|
| I can already see the people protesting against the creation of
| space marines.
| whycome wrote:
| No laws on mars
| vee-kay wrote:
| 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 wrote:
| 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 wrote:
| 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? htt
| ps://m.economictimes.com/industry/healthcare/biotech/heal
| ...
| vee-kay wrote:
| Hey, did you hear about the Volkswagen Monkeys?
|
| Volkswagen (the same megacorp that did the infamous
| Dieselgate/Emissionsgate scams) forced monkeys to inhale
| exhaust from its automobiles, to try to show that fumes
| from current models (the cars, not the monkeys) were less
| noxious than previous models.
|
| https://www.msn.com/en-us/science/sociology/20-of-the-
| most-u...
|
| https://en.wikipedia.org/wiki/Volkswagen_emissions_scanda
| l
|
| I guess this cannot be termed as "torturing animals" in
| the "name of science".
|
| We humans also inhale vehicular exhaust fumes, don't we?
|
| Oh wait, I forgot. Monkeys don't drive cars.
|
| Or do they? https://m.youtube.com/watch?v=XW5NLeGEo94
| a_better_world wrote:
| former practicing scientist at an institute whose name you
| would recognize.
|
| The field may not be fully constrained by ethics, which is
| just a way of saying that the work is done by people and
| people have varying ethical bounds, but from what I saw
| many of my colleagues were highly ethics driven.
|
| I remember one Russian colleague who smuggled blood
| products out of Russia so they could be tested for HIV.
| Because the Russian government refused to help these
| patients. The man risked his life to help HIV sufferers.
|
| Ethics is best when matched with courage, if a person is
| willing to put their life on the line for their beliefs.
|
| Also noting that in the western world, experiments
| generally need approval of an ethics board before
| proceeding. That board's sense of ethics might make
| different judgments than you on, for example, mice
| experiments, but there is a big difference between "not
| constrained" and "some of the constraints are different
| than what I would choose".
|
| where in this case, the ethics boards decided that provided
| a certain risk/reward barrier is crossed, and that the
| animals are otherwise treated well, sacrificing mice to
| improve human health is just fine.
|
| That is an ethics based decision that was debated for a
| long time. And maybe should continue to be debated, there
| is real value in your stance that all beings are sentient
| and this demands a level of care.
| vee-kay wrote:
| @a_better_world: (apt username for this conversation!)
|
| I do understand what you mean, and I do comprehend that
| animal testing cannot be avoided for scientific
| advancements to help and progress humanity.
|
| But I have a simple motto I want to adhere to (it is very
| hard though, to practice it in principle and action
| daily): Ethics is best when it is for the good of
| humanity, without being bad for Earth.
|
| In recent years, I am starting to feel humanity is
| sharply veering away from its basic ethics (and the first
| ethic must be to not shit where one eats - but hey, we
| are actively aggressively destroying the only beautiful
| bountiful planet we know of, that can support humanity),
| and doing whatever the top richest most-powerful elites
| want.
|
| And this unbridled greed and apathy is going to sow the
| seeds for the downfall of humanity, I'm afraid. At the
| cost of our precious Earth and its other denizens who
| share this planet with us humans.
|
| There has been a catastrophic 73% decline in the average
| size of monitored wildlife populations* in just 50 years
| (1970-2020), according to World Wildlife Fund's (WWF)
| Living Planet Report 2024.
|
| https://www.worldwildlife.org/news/press-
| releases/catastroph...
|
| https://www.bbc.com/news/articles/c5y3j0vzpl3o
|
| Forests around the world disappeared at a rate of 18
| soccer fields every minute, a global survey found.
|
| https://www.nytimes.com/2025/05/22/climate/deforestation-
| wri...
|
| Our generation is the last one that can still save the
| wild forests of the Earth, which help us cope with the
| climate crisis and preserve the biodiversity of the
| planet. A new study by Greenpeace Russia and the
| University of Maryland has shown that if urgent and
| effective measures are not taken to preserve wild
| forests, most of them will disappear in the next 20
| years.
|
| https://www.greenpeace.org/international/story/51810/wild
| -fo...
| vee-kay wrote:
| Is there a gene to avoid getting addicted to doomscrolling? ;-)
| vee-kay wrote:
| Relevant and topical..
|
| TikTok's 'Addictive Design' Found to Be Illegal in Europe:
| https://news.ycombinator.com/item?id=46911869
|
| Gen Z less intelligent than millennials: How skipping books
| and doomscrolling are taking a toll on cognitive abilities:
| says Dr. Jared Cooney Horvath: https://www.msn.com/en-
| in/news/India/gen-z-less-intelligent-...
| krzat wrote:
| Imagine if we could turn our bodies into perfect spheres, and
| then adjust genetic beauty preferences to match it.
| Windchaser wrote:
| Seems like a heat dissipation problem
| throwaway198846 wrote:
| There is no way it is just "just". And we should start from
| simpler stuff like vitamin B12, C and D.
| unsupp0rted wrote:
| 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.
| wartywhoa23 wrote:
| 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.
| jryb wrote:
| Paper: https://www.nature.com/articles/s41586-025-10006-0
| jurgenburgen wrote:
| 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?
| maxboone wrote:
| 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.
| krzat wrote:
| Cool. I wonder how long until we are able to steal anti-cancer
| genes from whales.
| trebligdivad wrote:
| That page numbers in books were only invented 50 years after the
| printing press is a fun snippet from the article
| swalsh wrote:
| Many times obvious things are only obvious once you see them.
| Like roller suitcases.
| bookofjoe wrote:
| See also: the wheel
| ssivark wrote:
| The early printing press was probably focused on short few page
| documents (an increasing scale), and it wouldn't be surprising
| if page numbers were a solution to help printers not mix up
| pages.
| adrian_b wrote:
| Your hypothesis does not match history, because the early
| printing was focused on things that had a potentially large
| market, which at that time meant books like The Bible, with a
| lot of pages.
|
| The parent article mentions that binding the pages of the
| first bibles in the correct order, in the absence of page
| numbers, was an extremely tedious work.
|
| That is why page numbers have invented many years later,
| exactly as you say, "to help printers not mix up pages".
| observationist wrote:
| The Gutenberg Bible was one of the first mass produced books
| - no page numbers on early copies.
|
| https://en.wikipedia.org/wiki/Gutenberg_Bible#/media/File:Gu.
| ..
|
| Hindsight is 20/20 , lol. There are so many obvious,
| effective constructs and functions in modern English, we
| kinda miss the absolute janky mess of hacking and tradition
| and arbitrary rules and facepalm moments that went in to the
| last 1500+ years of development, let alone the tens of
| thousands of years prior.
| mmooss wrote:
| > it wouldn't be surprising if page numbers were a solution
| to help printers not mix up pages.
|
| It's an interesting idea. Remember they printed large sheets
| containing many 'pages', I think even in different
| orientations, which were then folded and the ends cut to
| produce a nice orderly codex for the reader. They were
| printing in a different order than the one you read in.
|
| I do think they numbered the large sheets or similar, and you
| can find old books that retain that number, but I don't
| recall what it is called.
| observationist wrote:
| Sometime after 685 AD, they invented spaces between words. All
| text - in Latin to that point, mostly - was written in scriptio
| continua.
|
| All sorts of ambiguity and hilarity would ensue; to be a good
| writer, you needed to ensure that words didn't bleed together
| and form incorrect meanings in unintended combinations. If you
| lost your place when reading, you'd have to know generally
| where you were in a scroll, and restart from a place you
| remembered.
|
| Kinda crazy to think how difficult it would be to cross
| reference things and do collaborative research with no spaces
| or pages.
| datsci_est_2015 wrote:
| Also kind of crazy how long "but that's the way we've always
| done it" can remain the dominant system, despite a
| revolutionary change being so trivially achievable. This
| required absolutely no technological advancement, literally
| just putting a little more space between letters to reduce
| ambiguity.
| Ekaros wrote:
| English is good example. It has not been fixed for long
| while. Even if there would be so many better ways to write
| certain words.
| HappMacDonald wrote:
| I feel like Mathematical notation is also a great example
| (since Math is ultimately a separate language: the
| language of measurement)
|
| It's been built up over centuries where new innovations
| and shifts in perspective often create _new_ kinds of
| notation, but those most frequently just get tacked onto
| whatever else is already standard and the new notations
| almost never actually _supplant_ the old.
|
| AFAICT we haven't really had a big shift in fundamental
| mathematical notation in Europe (and its colonies) since
| Roman Numerals (CXXIII) gave way to Arabic (123) numerals
| four hundred years ago. 8I
| duskwuff wrote:
| > AFAICT we haven't really had a big shift in fundamental
| mathematical notation in Europe (and its colonies) since
| Roman Numerals (CXXIII) gave way to Arabic (123) numerals
| four hundred years ago. 8I
|
| Your history is a little confused. Arabic numerals came
| into use in Europe as early as the 13th century
| (introduced by Leonardo Fibonacci), but most other
| mathematical notation like "=" or or "[?]" didn't show up
| until the 16th or 17th century.
| wat10000 wrote:
| Imagine if it Turned Out that Capitalizing Various Words
| made Things more Readable. How Quickly Would That be
| Adopted?
| datsci_est_2015 wrote:
| Do you speak German? A language famous for capitalizing
| its nouns of course.
| wl wrote:
| Hittite was putting spaces between words in the 17th century
| BCE. And if we're just interested in Latin, it used the
| interpunct as a word divider hundreds of years before the use
| of the space as word divider happened. The use of scriptio
| continua despite knowledge of word dividers was a choice.
| observationist wrote:
| I wonder, how much was gatekeeping, keeping things hard on
| purpose, how much waas inertia, "that's just the way things
| are done", and how much was a kind of despairing "holy
| shit, it'd be so much work to have to go through and recopy
| everything in the new format, literally decades of effort,
| and there's other things we want to do with our lives".
|
| The whole context of written words had so much implicit
| process and knowledge and institutional memory, compared to
| now when we have petabytes of throwaway logs and trivial
| scratchpads for software running on a "just in case I might
| need to figure something out" basis. I'd love to see a
| written word graph over time, starting ~4k BC to now. And
| the complexity and diversity of those automated words are
| going up like crazy since LLMs.
| duskwuff wrote:
| Also probably a bit of "good parchment is expensive, why
| would we waste it on blank space?"
| mistrial9 wrote:
| yeah - under certain "the winners write the history"
| framework, I believe that scribes did not add spaces between
| "words".. However, the world is a big place; history is long.
| jjtheblunt wrote:
| i've had lots of Latin, know what you mean, but then thought
| of the Pantheon, where the word breaks (acronyms included)
| are indicated (with interstitial dots).
|
| https://commons.wikimedia.org/wiki/File:Pantheon_Rom_1_cropp.
| ..
| BurningFrog wrote:
| I can see how it wculd take that long to realize it would be
| nice to have a way to tell people which page to look at in
| their exact copy of a book.
| nullbyte808 wrote:
| Such a simple concept took this long to discover? Now we just
| need a way of packing the DNA strings into blank cells reliably.
| pc86 wrote:
| "just"
| ben_w wrote:
| > Now we just need a way of packing the DNA strings into blank
| cells reliably.
|
| Huh, I kinda assumed we'd already done that part with Dolly the
| sheep. But I'm not a biologist, I just saw headlines.
| oofbey wrote:
| They have a nice simple explanation. But the biochemistry of it
| I'm guessing is anything but simple. I've never heard of three
| way junctions in DNA before. I wonder how new those are. And
| designing the molecules to do the matching and splicing must
| have taken a long time.
| epistasis wrote:
| It's a lot like TikTok, right? It's a very simple concept:
| immediately produce customized video recommendations taking
| into account even the most recent interactions.
|
| You just need a way to pack the TikToks into blank data
| centers.
|
| (Note: blank data centers is a concept that kind of sorta makes
| sense. A blank cell doesn't make any sense at all)
| Metacelsus wrote:
| It was known in 2006 but rediscovered recently:
| https://patents.google.com/patent/US20060281113A1/en
| jycnaw wrote:
| 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.
| jackconsidine wrote:
| 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
| biophysboy wrote:
| 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.
| codesnik wrote:
| pcr amplifies all sequences, correct or wrong, no? and as I
| understand it, it works on short snippets the best.
| biophysboy wrote:
| 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.
| bookofjoe wrote:
| Kary B. Mullis Nobel Prize lecture Nobel Lecture, December
| 8, 1993
|
| The Polymerase Chain Reaction
|
| https://www.nobelprize.org/prizes/chemistry/1993/mullis/lec
| t...
| oofbey wrote:
| Intuitively I agree some kind of selective amplification should
| be able to correct for the mistakes. But I think it will be
| complicated. Because the filtering process needs to be much
| more complex. It can't just chemically match to a known
| subsequence - you won't know where the mistake might be in a
| long sequence.
| biophysboy wrote:
| This is a good point. WXYZ and WYXZ are indistinguishable via
| PCR. And the possibilities accumulate with more segments.
| mbreese wrote:
| I don't think PCR is necessarily relevant here. I had the
| impression that this would be lost useful at linking multi-kb
| fragments together. If we are looking at sizes much above 2kb,
| PCR is going to struggle to generate full length fragments
| efficiently.
|
| I didn't see this technique as having DNA modification per-se,
| but a novel way to managing the hybridization process. It's
| stock (well engineered) oligos, if I read it correctly.
| Kirr wrote:
| Very cool, but may have some unexpected consequences. E.g.,
| someone can probably use this to synthesize a bacterial genome
| containing every known drug resistance gene, and this is just the
| first thing that comes to mind. Possibilities for bioeconomy
| indeed.
| jryb wrote:
| You don't need to synthesize an entire bacterial genome from
| scratch to do this. You can just insert them one at a time into
| existing bacteria. Or just give them plasmids. Anyway, the
| ability to achieve the outcome you're describing has existed
| for decades.
| GlibMonkeyDeath wrote:
| What really blows my mind about this is that they are using off-
| the-shelf T4 Ligase to ligate the junctions. I figured this was
| going to be some tour-de-force of enzyme engineering, but nope,
| all the reagents are pretty much commercially available.
|
| It is super clever and exciting. Note that people have been able
| to assemble short (<100 bases) DNA oligomer fragments of
| synthetic DNA into longer fragments using "splint" oligos since
| forever. But in this case, each splint has to be custom
| engineered to only bind to the junction of interest (in practice
| it is pretty tricky and expensive to do this.) These guys figured
| out a way to use engineered sequences to make the match, and used
| a clever (but also more or less standard) way to chew up the
| engineered stuff, leaving behind only the desired long assembly
| with no scars at the end of the process.
| pcrh wrote:
| Yes, it's very elegant! It's one of those things you wish you
| had thought of yourself. Kudos to these guys for being first.
| victor106 wrote:
| For someone in Software what is a good way to learn the
| fundamentals of this?
| zulko wrote:
| Possibly not what you're asking for, but I wrote a generally-
| accessible intro to why it can be tricky to assemble many DNA
| fragments with "Golden Gate Assembly", a mainstream method
| which relies on short sequence overhangs. The Sidewinder method
| discussed in this thread aims to solve that "short overhang"
| problem.
|
| https://zulko.github.io/bricks_and_scissors/posts/overhangs/
| vikramkr wrote:
| If you live near a community bio lab see if you can join up and
| take some classes to learn some basic lab techniques. And some
| sort of intro bio class via mooc/textbook/local college class
| whatever if you can but community lab is honestly a great place
| to start if you have one.
|
| The main thing to keep in mind is that all the stuff that
| involves analogies between software and biology is almost
| universally a bullshit oversimplification that you can safely
| ignore. It's just that software is so profitable and there's so
| much vc money in it that there's a ton of pressure to be like
| "oh we can program biology like we program computers." We can't
| - we invented computers but didn't invent biology. Biology is
| the end result of 4 billion years of unchecked entropy - it's a
| chaos system, non deterministic in the wildest ways, impossibly
| complicated, and yet something we are getting astonishingly
| good at understanding and engineering.
|
| Basically, all the biologists that started companies that were
| like "we can program biology like we can program computers" are
| bankrupt now.
|
| On the other hand, the computer scientists that respected the
| nature of biology and pushed the limits of computing to develop
| Alphafold - giant models trained on the full complexity of
| biological data - finally created computer systems that could
| handle biological systems like protein folding at an
| extraordinary level of capability. They won a nobel.
| ramon156 wrote:
| Follow up question (Not OP), would alphafold more be used to
| experiment with an already-defined theory that you have, or
| could you also make some toy projects (e.g. how people make
| projects around trading engines).
|
| I'm wondering if I could find a fun weekend project in
| alphafold just to see what it's like.
| elric wrote:
| TIL community biolabs are a thing ...
|
| Are they really? Is this just limited to some very specific
| areas with an active biotech scene?
| cess11 wrote:
| In my part of the world it is a common thing among high
| schoolers, which form associations and use labs at school
| or a local university.
|
| It's not uncommon that adults do something similar and run
| a community workshop with whatever the members are
| interested in.
| oytis wrote:
| Could we better not?
| daemonk wrote:
| Pretty cool technique using complementary overhangs and toehold
| sequences to generate a 3-way heteroduplex, ligate knick, and
| then remove barcode duplex.
|
| They don't give much details on how the barcode duplex is removed
| though. I guess ultimately the barcode duplex strands can just be
| melted off and the ligated strand can be used to template off of.
|
| If this can be made into an easy to use kit, can really make
| vector generation much easier and hopefully not locked into
| proprietary systems.
|
| I can imagine a company that bioinformatically generates
| libraries of common long oligos with corresponding barcode and
| allow end-users to select oligos to modularly ligate together in
| a one pot reaction. Cool stuff.
| omnicognate wrote:
| > using complementary overhangs and toehold sequences to
| generate a 3-way heteroduplex, ligate knick, and then remove
| barcode duplex
|
| At first I thought this was about olympic figure skating, but
| after a bit of googling I _think_ :
|
| Complementary overhang -
| https://en.wikipedia.org/wiki/Sticky_and_blunt_ends
|
| Toehold sequences:
| https://en.wikipedia.org/wiki/Toehold_mediated_strand_displa...
|
| Ligate (ligase?) knick (nick?) -
| https://en.wikipedia.org/wiki/Nick_(DNA)
|
| Barcode - https://en.wikipedia.org/wiki/DNA_barcoding
|
| Heteroduplex - https://en.wikipedia.org/wiki/Heteroduplex
| mbreese wrote:
| We've been able to do this type of nucleotide 3D engineering
| for a while. I used to use large DNA branched complexed
| fluorophores to label cDNA back when I was in grad school. They
| were more or less mixed of DNA that self assembled into larger
| hairballs.
|
| But branched DNA is really interesting. It's a bit hard to get
| my head around. We spend so much time thinking about DNA in the
| 2D sequence sense, it's easy to forget that it exists in 3D
| space.
|
| I'm honestly not sure how different this really is to the
| traditional ways of doing this (with custom oligos). The common
| set of large self-hybridizing oligos is definitely easier, but
| you still have to have compatible tag overhangs between your
| two fragments. Meaning, it isn't quite as universal and you'll
| still need work to pair the fragments together. But where I
| think it might be useful is if you have a set of common
| hybridizing pairs that can be easily located onto the custom
| flanking oligos. You'll still need some sequence analysis to
| get your custom oligos, but it would make the process more
| "standardized".
|
| I think the main bonus here is the self correcting selection...
| that you only end up with matching pairs linking together, so
| you could really have a mix in a one tube reaction that links
| many kilobase fragments together. That's quite nice. And
| useful. And still cool.
|
| One thing that is interesting is that this is another step
| towards getting the "writing" step of DNA analysis better. For
| the past 50+ years, we've developed all sorts of tools for
| reading DNA. It's only really been the past 20-ish or so that
| we've had tools for writing. And now we can write longer
| chunks. That's all a good thing.
|
| Not sure I think it's revolutionary (yet), but that's a
| university PR release for you! I'm still thinking about the
| paper.
| koeng wrote:
| I work in DNA assembly and synthesis. Here is my take:
|
| They don't use oligo pools - "This capacity may be adapted to use
| large oligo pools to substantially reduce the cost per
| construct45 but requires further engineering to account for the
| formation of the unintended Sidewinder heteroduplexes before
| assembly and the higher truncation rate of pooled oligos"
|
| This absolutely destroys any unit economics when it comes to DNA
| synthesis. Oligo pool synthesis isn't 10x cheaper, it's 100x to
| 1000x cheaper than individual oligo synthesis.
|
| So what they really have is a good way to do DNA assembly from
| synthesized oligos; fair. But we have that: GoldenGate can do 40
| part assemblies, hell it can do 52 part assemblies, and you CAN
| use oligo pools -
| https://pmc.ncbi.nlm.nih.gov/articles/PMC10949349/ (there are a
| couple enzymatic properties which allow this, mainly that you can
| use full doublestranded DNA, which you can make with a PCR. Can't
| make these overhang guys with a PCR).
|
| We've even found that with some GoldenGate enzymes, the biology
| somehow breaks the current models of the physics of ligation by
| being so efficient -
| https://www.biorxiv.org/content/10.64898/2026.01.31.702778v1
|
| Their gels do look really good, I'll admit. I can imagine
| circumstances (exception cases) where this would be better. But
| not only is this kind of thing for 99% of cases has already been
| available for many years while being orders of magnitude cheaper
| (plural).
| 1vuio0pswjnm7 wrote:
| Here's the paper without the cookies
|
| https://web.archive.org/web/20260121201045if_/https://www.na...
| Metacelsus wrote:
| The Church lab came up with this in 2006, sadly it never took
| off: https://patents.google.com/patent/US20060281113A1/en
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