6 ms·

What I would like to know, and haven't heard talked about in any of these articles yet, is if it's possible to substantially alter the genome of an already livi

What I would like to know, and haven't heard talked about in any of these articles yet, is if it's possible to substantially alter the genome of an already living creature. This article touches on it briefly at the beginning, but doesn't elaborate on the idea: > This means it’s possible to create genetically modified plants or animals of practically any species, as well as to modify the cells of adult organisms, including humans. But so far, I've seen every article go to great lengths to avoid a very obvious question. Aside from medical cures, is it possible to use this technology for cosmetic purposes? Will I be able to change my eye color permanently? Cure baldness in adult humans? Alter metabolism?

napo 11y ago
If you want to alter the genome of an already living creature I guess that you have to change every cells. I'm not sure if it's possible. However, a virus seems to be the perfect tool (it modify your genome to copy itself and infect other cells).
- tdaltonc 11y ago
  You only need to alter it in the cells you care about.
- ldehaan 11y ago
  DNA doesn't vary by cell, and the method of introduction is chemical, I imagine this creates a chained effect, otherwise how would cells pass on activated chains through the body when your DNA naturally changes.
  - toufka 11y ago
    The DNA of a body does not naturally change (in any organized way). Cells pass on changed DNA only to their progeny. Only genetic changes to gametes will be passed on genetically to children. However, the regulation of DNA can be transmitted. One can turn genes on and off throughout the body by exposing the cells to particular signals such as hormones. But those don't change the DNA, they just change the interpretation and usage of the DNA that's already present.
  - eggie 11y ago
    The DNA does vary cell by cell. How does cancer come about if not?
    - pmalynin 11y ago
      Radiation. Mutagenic chemicals. Transcription errors. Even viruses. Not anything natural to the human body e.g. it does not change without external influences.
epicureanideal 11y ago
This is already being done. See the CEO of BioViva doing this to herself. Apparently it only gets introduced into 5-60% of cells at this point, but that's a great start.
- Jtsummers 11y ago
  http://www.technologyreview.com/news/542371/a-tale-of-do-it-yourself-gene-therapy/ http://www.technologyreview.com/news/542371/a-tale-of-do-it-... Had to look up what you referenced, hadn't heard about this before. Side note: I find it amusing that two main people in this article are the CEO (Parrish) and a researcher (Church), and a man named Fossell is an anti-aging researcher.
tdaltonc 11y ago
These methods absolutely can alter genes in adult cells, if they can get in to them. The difficulty would be in designing the vector. How do you get the edit commands in to the right cells and only the right cells? When we do this in animals we use purpose built viruses to deliver the payload. But it involves a lot of trial and error and it doesn't always take. That's fine for animals, less so for humans.
toufka 11y ago
>if it's possible to substantially alter the genome of an already living creature. Yes, but it's tricky right now. The delivery mechanisms are still rough. But for certain applications, in certain tissues, for certain kinds of diseases it is being done today (see Sangamo getting cleared for a gene therapy for hemophilia last week)[1]. Currently we have two ways to direct a genetic payload - one is localized (cellular) control of the actual delivery mechanism, the other is (biologically-relevant) temporal control of when the payload gets 'fired' or used. Practically, we can strip some kinds of mammalian viruses of their own payload (and their ability to replicate), and utilize their own DNA insertion machinery (which is very nicely evolved to match our physiology) to insert a desired payload into the genome of a live organism. Some tissues are better at receiving specific payloads than others. (If you find a tissue and corresponding virus that delivers a tissue-specific viral infection, we can likely deliver a tissue-specific viral gene therapy to that tissue.) Once the genetic payload is loaded into the genome we have other ways to control when the payload is actually turned on. We can make the payload sensitive to tissue-kind, or biological timing events, or sensitive to other kinds of biologically relevant environmental cues. Both of these methods alone, however, are generally leaky. If the changes you are making are critical either for effect, or for preventing off-target effects, then these two methods alone are likely insufficient for a general population therapy to not be a dangerous gamble. The consequences of injecting the wrong code (or the right code to the wrong place) can be fairly catastrophic (induced, and immediate cancer). And that is precisely why a good 'text editor' is valuable. One intervening point is that most viruses inject their payload into your genome randomly. And if they happen to overwrite some required genetic code of yours they cause cancer. Some viruses actually intentionally overwrite the code for your viral defense mechanisms (see HPV overwriting the P53 gene). In general, random injection of genetic payload into a live organism's genome (source code) is a bad idea. The ability to have a good 'text editor' means we can now ensure that if the payload gets to the desired cells, then we can insert that payload into the genome in a desired location that is unlikely to cause problems. And since we can further regulate when the payload is fired, we now have 3 levels of control ( 1: localized cellular delivery, 2: localized genetic insertion, 3: biologically controlled activation). And those three levels together can significantly reduce the chance of mis-editing a live organism's genome. Once these three regulatory mechanisms are made safe enough to not just be used in situations where risk/reward ratio is skewed by the lethality a disease, there is no reason they cannot also be used for an arbitrary biological effect. [1] http://investor.sangamo.com/releasedetail.cfm?releaseid=944828 http://investor.sangamo.com/releasedetail.cfm?releaseid=9448...
grondilu 11y ago
Altering the genome of an already developed organism, that is as opposed to an egg-cell or an embryo, is, I suppose, much more difficult. It may be possible though, and if so, it does represent tremendous therapeutic possibilities, but in the grand scheme of things, I believe it's less important than the possibility of editing organisms "from scratch", that is immediately after fecundation (or even before, as I recall an article about using gene editing on sperm cells [1]). Therapeutic prospects matter to us from a selfish, subjective point of view but from an objective, anthropological point of view, the idea that we could create organisms with an arbitrary genome is much more significant. 1. http://www.technologyreview.com/news/543541/how-to-really-engineer-a-human-baby/ http://www.technologyreview.com/news/543541/how-to-really-en...
ldehaan 11y ago
Here is a Ted talk that addresses those questions and more: We can now edit our DNA. But let's do it wisely http://www.ted.com/talks/jennifer_doudna_we_can_now_edit_our_dna_but_let_s_do_it_wisely http://www.ted.com/talks/jennifer_doudna_we_can_now_edit_our...
jhallenworld 11y ago
>is it possible to substantially alter the genome of an already living creature? Roy: I want more life, fucker (father). Tyrell: The facts of life: To make an alteration in the evolvement of an organic life system is fatal. A coding sequence cannot be revised once it's been established. Roy: Why not? Tyrell: Because by the second day of incubation, any cells that have undergone reversion mutations give rise to revertant colonies like rats leaving a sinking ship; then the ship sinks. Roy: What about EMS recombination? Tyrell: We've already tried it. Ethyl methane sulfonate is an alkylating agent and a potent mutagen. It created a virus so lethal the subject was dead before he left the table. Roy: Then a repressor protein that blocks the operating cells. Tyrell: Wouldn't obstruct replication, but it does give rise to an error in replication so that the newly formed DNA strand carries a mutation and you've got a virus again. But this - all of this is academic. You were made as well as we could make you.

napo 11y ago

If you want to alter the genome of an already living creature I guess that you have to change every cells. I'm not sure if it's possible. However, a virus seems to be the perfect tool (it modify your genome to copy itself and infect other cells).

tdaltonc 11y ago
You only need to alter it in the cells you care about.
ldehaan 11y ago
DNA doesn't vary by cell, and the method of introduction is chemical, I imagine this creates a chained effect, otherwise how would cells pass on activated chains through the body when your DNA naturally changes.
- toufka 11y ago
  The DNA of a body does not naturally change (in any organized way). Cells pass on changed DNA only to their progeny. Only genetic changes to gametes will be passed on genetically to children. However, the regulation of DNA can be transmitted. One can turn genes on and off throughout the body by exposing the cells to particular signals such as hormones. But those don't change the DNA, they just change the interpretation and usage of the DNA that's already present.
- eggie 11y ago
  The DNA does vary cell by cell. How does cancer come about if not?
  - pmalynin 11y ago
    Radiation. Mutagenic chemicals. Transcription errors. Even viruses. Not anything natural to the human body e.g. it does not change without external influences.

epicureanideal 11y ago

This is already being done. See the CEO of BioViva doing this to herself. Apparently it only gets introduced into 5-60% of cells at this point, but that's a great start.

Jtsummers 11y ago
http://www.technologyreview.com/news/542371/a-tale-of-do-it-yourself-gene-therapy/ http://www.technologyreview.com/news/542371/a-tale-of-do-it-... Had to look up what you referenced, hadn't heard about this before. Side note: I find it amusing that two main people in this article are the CEO (Parrish) and a researcher (Church), and a man named Fossell is an anti-aging researcher.

tdaltonc 11y ago

These methods absolutely can alter genes in adult cells, if they can get in to them. The difficulty would be in designing the vector. How do you get the edit commands in to the right cells and only the right cells? When we do this in animals we use purpose built viruses to deliver the payload. But it involves a lot of trial and error and it doesn't always take. That's fine for animals, less so for humans.

toufka 11y ago

>if it's possible to substantially alter the genome of an already living creature. Yes, but it's tricky right now. The delivery mechanisms are still rough. But for certain applications, in certain tissues, for certain kinds of diseases it is being done today (see Sangamo getting cleared for a gene therapy for hemophilia last week)[1]. Currently we have two ways to direct a genetic payload - one is localized (cellular) control of the actual delivery mechanism, the other is (biologically-relevant) temporal control of when the payload gets 'fired' or used. Practically, we can strip some kinds of mammalian viruses of their own payload (and their ability to replicate), and utilize their own DNA insertion machinery (which is very nicely evolved to match our physiology) to insert a desired payload into the genome of a live organism. Some tissues are better at receiving specific payloads than others. (If you find a tissue and corresponding virus that delivers a tissue-specific viral infection, we can likely deliver a tissue-specific viral gene therapy to that tissue.) Once the genetic payload is loaded into the genome we have other ways to control when the payload is actually turned on. We can make the payload sensitive to tissue-kind, or biological timing events, or sensitive to other kinds of biologically relevant environmental cues. Both of these methods alone, however, are generally leaky. If the changes you are making are critical either for effect, or for preventing off-target effects, then these two methods alone are likely insufficient for a general population therapy to not be a dangerous gamble. The consequences of injecting the wrong code (or the right code to the wrong place) can be fairly catastrophic (induced, and immediate cancer). And that is precisely why a good 'text editor' is valuable. One intervening point is that most viruses inject their payload into your genome randomly. And if they happen to overwrite some required genetic code of yours they cause cancer. Some viruses actually intentionally overwrite the code for your viral defense mechanisms (see HPV overwriting the P53 gene). In general, random injection of genetic payload into a live organism's genome (source code) is a bad idea. The ability to have a good 'text editor' means we can now ensure that if the payload gets to the desired cells, then we can insert that payload into the genome in a desired location that is unlikely to cause problems. And since we can further regulate when the payload is fired, we now have 3 levels of control ( 1: localized cellular delivery, 2: localized genetic insertion, 3: biologically controlled activation). And those three levels together can significantly reduce the chance of mis-editing a live organism's genome. Once these three regulatory mechanisms are made safe enough to not just be used in situations where risk/reward ratio is skewed by the lethality a disease, there is no reason they cannot also be used for an arbitrary biological effect. [1] http://investor.sangamo.com/releasedetail.cfm?releaseid=944828 http://investor.sangamo.com/releasedetail.cfm?releaseid=9448...

grondilu 11y ago

Altering the genome of an already developed organism, that is as opposed to an egg-cell or an embryo, is, I suppose, much more difficult. It may be possible though, and if so, it does represent tremendous therapeutic possibilities, but in the grand scheme of things, I believe it's less important than the possibility of editing organisms "from scratch", that is immediately after fecundation (or even before, as I recall an article about using gene editing on sperm cells [1]). Therapeutic prospects matter to us from a selfish, subjective point of view but from an objective, anthropological point of view, the idea that we could create organisms with an arbitrary genome is much more significant. 1. http://www.technologyreview.com/news/543541/how-to-really-engineer-a-human-baby/ http://www.technologyreview.com/news/543541/how-to-really-en...

ldehaan 11y ago

Here is a Ted talk that addresses those questions and more: We can now edit our DNA. But let's do it wisely http://www.ted.com/talks/jennifer_doudna_we_can_now_edit_our_dna_but_let_s_do_it_wisely http://www.ted.com/talks/jennifer_doudna_we_can_now_edit_our...

jhallenworld 11y ago

>is it possible to substantially alter the genome of an already living creature? Roy: I want more life, fucker (father). Tyrell: The facts of life: To make an alteration in the evolvement of an organic life system is fatal. A coding sequence cannot be revised once it's been established. Roy: Why not? Tyrell: Because by the second day of incubation, any cells that have undergone reversion mutations give rise to revertant colonies like rats leaving a sinking ship; then the ship sinks. Roy: What about EMS recombination? Tyrell: We've already tried it. Ethyl methane sulfonate is an alkylating agent and a potent mutagen. It created a virus so lethal the subject was dead before he left the table. Roy: Then a repressor protein that blocks the operating cells. Tyrell: Wouldn't obstruct replication, but it does give rise to an error in replication so that the newly formed DNA strand carries a mutation and you've got a virus again. But this - all of this is academic. You were made as well as we could make you.