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Better Gene Editing than CRISPR

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George Church describes going beyond cutting DNA to precise editing.

1. Phage Integrases (Protein and DNA)
2. TAL Deaminases (custom Protein)
3. Chemical Targeting (custom polymer)
4. lambda (λ)-red recombinase (Custom DNA)

Beyond editing to writing large genomes

DNA-based target recognition

For DNA-based target recognition systems, the two major approaches, multiplex automated genome engineering (MAGE) using λ-red recombination and conjugative assembly genome engineering (CAGE) have been widely used in prokaryotes and demonstrated a high degree of multiplexability. Briefly, the λ-red system, similar to recET, originates from phage and when imported into bacterial cells, can stimulate high levels of recombination in the presence of homologous DNA. Although the machinery used in these approaches has not been fully optimized yet for eukaryotic cells, some conjugal transfer has been demonstrated and use of an optimized version of Redβ in human cells has yielded limited success. Moreover, these technologies can be used to edit and propagate large pieces of DNA in bacteria for eventual use as donor DNA molecules for HR in human cells.

104 thoughts on “Better Gene Editing than CRISPR”

  2. Right, more than one year, each year. I said that. But only each year until a real breakthrough is made. For example, we don’t really spend too much time trying to figure out how to chip better stone tools anymore. Research in that department was overrun by events when metallurgy came along.

  5. No, they don’t. They like interventions which prop up the economy long enough for them to move their money.

  6. Always, ALWAYS, check the spelling and grammar in a sentence where you are insulting someone else’s intelligence.

  7. “all a biological singularity requires is increasing life expectancy by more than one year, each year”

    AND to be able to maintain that rate of growth indefinitely.

    Use of the term “actuarial escape velocity” is rhetorically dishonest because it smuggles in the vision of acceleration occurring above the atmosphere, where there is no friction to slow you down. In reality pushing back technological boundaries tends to often run up against new problems that slow progress right down again, often for decades.
    See how aircraft speeds didn’t exactly keep shooting up after the development of the SR-71.

  11. A healthy person who can become young again if they want to but wants to be old and get a pension will have much the same sympathy as someone who keeps claiming sick days because they are hungover.

  14. Wasn’t it Aubrey de Grey that said that anyone (presumably with the means to afford it) that can make it to 2045 might never die of old age? He might not be right . . . but he might not be wrong.

    Bear in mind that all a biological singularity requires is increasing life expectancy by more than one year, each year. For those on the leading edge, this buys time for the further advancement of age reversal technologies, and at some point most diseases of old age cease to matter. Further, if the body is really kept at a young state, then concern about hypothetical old age diseases which might occur at ages longer than humans currently live (approx. 120 years) would be rendered moot.

    The main fly in the ointment I see is that our minds (not our brains), like computer operating systems, may not be able to continue operating past some age and, unlike our computers, we don’t have any idea how to do a hot restart or, if we could, whether that wouldn’t be analogous to death.

  15. Yup, I foresee pension funds eventually offering a rejuvenation treatment and (maybe) a cash settlement in exchange for your pension. Long before that happens you won’t find any employers that still offer pensions. If you refuse the rejuvenation, they will still dump you, although maybe with a larger cash settlement.

  16. “you can’t go backwards in time to a younger state… ”

    Actually, I believe there is a jellyfish (Turritopsis dohrnii) that does exactly that.

  17. No, there is no way to “save the day”.  That there would be an economic contraction was a certainty.   But not doubling down on what Hoover did and quadrupling down on the stupid like FDR did would have meant it was recovered from within a year the way the previous recession was.

    What made “Japan’s Lost Decade” lost is why the Great Depression lasted so long and there was no perceivable recovery from 2008 under Obama — government attempts to not have the mistakes of the past have their effect on the future.

  19. It’s not that ‘old age lasts longer,’ but that we’ve beaten most of the infectious threats and some of the system failures that kept you from getting there at all.

    It doesn’t work like Tithonus. The things that make you ‘old’ *are* the things that ultimately kill you. You can’t fix them and still look/feel like a nominal (say) 100.

  20. Umm…I think I’ll wait until 2030. Let the ‘early adopters’ put their lives on the line, first.

  23. Unity Biotechnology and Oisin Biotechnology have senescent cell clearance therapies now but have to conduct five year safety trials, so it will be 2023, and 2024, and possibly 2025 for these 45 age related gene therapies.

  24. A) Where’d you get the stupid idea I’m geriatric?

    B) The world needs a turn to Liberty quite badly, it’s the only way to stop the would be mass-murders.

  25. No, the Great Depression shows the bad side of socialism–it was only Great because of socialist policies in response to it.

  26. That’s because you have nothing sensible you could say in objection. Democrat policies have lead us into $220tn in unfunded public liabilities, a good $18 of which are in the programs you defended. Most of that front loaded into the next few decades. What cannot continue will stop, the question is whether it will be planned for and of minimal disruption.

    Math works.

    You can’t stop that. It doesn’t matter how many votes you fake.

  27. Maybe, but there are so many fewer of them. And really in any klutch of klansters, 9 of ten will be some type of government agent or informant…

  29. Venezuela shows the bad side of socialism,
    the Great Depression showed the bad side of capitalism. I really dont know which was the worse.

  30. Unfortunately many billionaires dont become such until they inherit.
    Young billionaires with some sense are surely funding mr.

  32. Remember, Robert Heinlein wrote a series of books about a character named Lazarus who had been bred for longevity rather than intelligence with the idea being that by the time we really accumulate enough experience to be useful …we die.

  35. Its referencing nicotinamide riboside or nicotinamide mononucleotide which are more expensive – not regular stuff.

    But yes even then, it is $50 a gram now, not $1600!

  37. Ya, they are aren’t they? Right now they are calling everyone not like them racist and 99% as*holes .. can you imagine their lack of self awareness! Why can’t they be as cool and knowledgeable as us?

  38. Go away son, the world doesn’t need your geriatric a$$, your white privilege and hopes to return to the times of a better yesteryear is dying out.

  39. One would think racist conservatives tend to be more so, and especially considering 99% of them are assh*les.

  41. And a ww2-style taxation, with the money spent warring against death, with the whole world on it, could give us a lot more than what it would cost.

  42. And they should be nuked*.  They are unconstitutional and so illegal, illegitimate steps down the path to what Venezuela is now, the endpoint of pretending government is a way to live at everyone else’s expense.

    BTW, Socialist Insecurity and Medicare are how the old are attacking the young.

    Ether you pay your own way, you get by or don’t on honest charity–or like you, you are a thief voting yourself into someone else’s pocket.

    *Which is to say, discontinued going forward for all new enrollees, pro-rated by age for existing involuntary particpants, payroll taxes rolled into the income tax, payouts means tested, and payouts acknowledged to be coming from the general revenue as they have in principle been ever since the Johnson administration went to unified budgeting.  The income tax itself should have no deduction but a standard one per payer & dependent, and a flat rate.

    We can do at least as good a job of it as Chile.

  46. There was no informed promise of early fusion only hope. The science wasn’t even worked out until the 80s, so it doesn’t matter what they were told or what they believed. The only fusion project capable of working based on the science that was worked out in the 80s is ITER, no other reactor project is capable of net fusion on paper.
    …
    After they reach a certain age, it much to late for major funding boosts to matter in time for them. They will only suceed in proving themselvs unfit to survive in the long run, they should have made better choices.

  47. The only promises of age reversal heretofore were those of men in dresses peddling magics and seeking donations.

  48. Example 8 leaves me with questions:

    1. Why is #8 first, before #1 or #5?
    2. Why is nicotinamide listed at $1600/g? When I look at my local supermarket I can buy 30 grams for $7.95?

  49. What choice? You don’t get retirement benefits at all until you’ve proved that rejuvenation isn’t an option for you.

  51. Once the average billionaire/senior government type starts to believe that research now will be producing useful treatments soon enough for them to actually benefit: THEN you’ll see major funding boosts.
    Until then this is just one of dozens of different schemes promising the world but little distinguishable from similar claims made 50 years ago. (See fusion)

    No. Don’t try to convince ME that its different this time. I mean what is the average senator or super-property-developer going to see that is different this time.

  53. They’re trying to nuke Medicare and Social Security now so I don’t I don’t think it’s a stretch.

    PS What’s with this GreenBrownie garbage if you can’t even use a valid Id then you have no right to criticize others….

    Update: Tom below gave an excellent example of the right wingers and how they think (I’m not imaging them or what they want to do) so no, I’m not going to give it a rest.

  56. First off, I’m not sure sure that’s really true, medicine has gotten better dealing with the chronic diseases of the old but that’s about it. Even if it was true, this would still requires that seniors don’t experience cognitive decline. Now assuming that both of those are true it’s still basically impossible to find such jobs for seniors and you’d alienate a lot of younger workers with quotas or lower age limits on certain jobs… you’d have the right wingers attacking seniors the way they do minorities that receive affirmative action.

  57. ahh…what if you are simply given the choice of retire as now live a few years and then die or option two rejuvenate on guv’s dime with the understanding you must keep working/paying taxes?

  60. More plumbers is more useful than more lawyers. One group removes problems. And yes if you are good at welding stainless steel we might have an high flying position for you if you are not afraid of height 🙂

  63. Old people today are way more active and healthy than an generation ago. No they can not do heavy manual work but that is just an tiny faction of the workforce today. Work who require it like construction and lumberjacks, rotate older workers into machine operators or management.

  64. Bet if you could somehow determine it you would find that 90% of all the progress the human race has made throughout history could be attributed to roughly ten thousand people, out of all the billions who have lived and died. George Church would likely be one of those people.

  65. but it was in a few years grasp. It was merely a theoretical possibility to be researched and reached some 30-50 years in the future. And 30 was the most optimistic, if not reckless POV…

  66. “hopefully most of the lunatic demorats will not be able to afford these treatments and will not be able to prolong making the world a more terrible place than it need be.” – there, fixed it for you.

  68. If you want to maximize your chances of reaching the cutoff, you should become vegetarian and do it properly. Also, try and eliminate all voluntary life threatening risks from your life.

    You will have to work for it If you want to live for as long as you care to.

  69. “Delivery of 45 Age Reversing Gene Therapies at Once is Under Peer Review”, so where is the link in this material to that claim?

  71. Nothing wrong with that. I think of it as a digital reincarnation cycle. More possibilities for fun that way anyway.

  72. We can’t be certain this is true but… right now we’re children with a very limited perspective of the universe, so it’s silly to be pessimistic. Maybe a superhuman mind running on quantum computers for billions of years will find a solution to allow truly infinite computations. Or maybe it will create a solid logical proof about a meaning to life which negates the need for an infinite linear existence. Whatever it comes up with, the thinking would so far dwarf what we can do at the moment, that for now we might as well just plan for our immediate survival and a few thousand years of fun. The rest can wait.

  73. Many people i know can easily afford such treatments, I bet prices will be extremely high until the 1% market is saturated. They’re all interested in such progress, but they tend to support decisions that are more likely to hinder such progress. You would think living a much longer and healthier life would be one of their more important goals and people would thus priorities above much less important ones.

    Progress is slow because most people prioritize more immediate, but less important goals over the more long term and more important ones. The idea being there will be lots of time to sort out the long term stuff, but timing technological developments isn’t something you should bet your life on.

    How many Billionaires start funding related medical research with their pocket change when they’re 40 vs when they’re 60?

  74. Think government debt is bad now?

    Just wait until social security and Medicare have to pay for people to stick around for an extra decade or two.

    Plus state and federal employee pensions…

  75. Hopefully, most of the deplorable people will not be able to afford these treatments and will not be able to prolong making the world a more terrible place than it need be.

  76. I’ve been following it for decades, too. Actually have a first edition of The Immortalist, read it when I was a senior in high school. And it hasn’t always been five or six years into the future, that’s only recently. It used to be a LOT more distant a prospect.

    The progress hasn’t been coming as fast as I’d have liked, but it IS being made.

  77. No, inflection points are different. The “knee” in an English idiom for a particular point in a curve, roughly where, if you did a piecewise linear approximation of the curve you’d switch from one piece to another.

    It’s not well defined, of course.

  78. They should call it “disease reversal” therapy not “age reversal”… you can’t go backwards in time to a younger state… only patch up an aging machine so that it works longer…. if a gear is going bad you fill in the cracks… it’s hardly age reversal… if you want to live forever there’s more promise mapping biological nueral patterns into artificial intelligence where you can simply move your consciousness from one vessel to another when the old one wears out… of course there might actually be limits on how long an artificial intellegence can live without going insane… then you have to keep pruning memories and hitting reset

  84. Indeed that is the case but we have to hope that these treatments do more than make old age last longer (which is all we’ve done to date.)

  86. Leftist catastrophists seeking to justify more government intervention and central direction hardest hit…

  87. If I live long enough to see the end of the universe I would have the technology to
    1 – reverse time
    2 – jump to another universe

  89. These therapies, if they pan out, would give us a few years or decades.

    From barely longer but statistically measurable ones, to super-human life spans, but not indefinite ones.

    But science marches on, of course, and the first wave of verifiable senescence therapies will foster a lot more research and better ones.

  92. Yeah. There was a Bloomberg article yesterday about the demographic decline and how its supposed to be a problem in the future. It looks like life extension is showing up just in time.

  93. Yes, but if I’m around in some form long enough to worry about proton decay (if they indeed do), or see the last supermassve black hole evaporate (after which pretty nothing of note will happen in the universe), I’ll use my last thought to call that a pretty good run…

  95. I can’t see senescent cell elimination on the list. Maybe it’s also required for a complete rejuvenation cocktail?

  97. There are interesting social implications of increasing lifespan. For instance, the number of births per year per person for a stable population will need to decrease.

  101. The knee you speak of in the curve is relative to time span. The longer the observers life span the faster the curve will seem. While a person born on the curve it will seem slower.

  103. Six years out? I might still be around by then.

    Maybe we’re finally reaching the knee in the curve, where the exponential drastically departs from a linear projection? That would be nice.

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