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Adding New DNA Letters Make Novel Proteins Possible (economist.com)
An anonymous reader quotes a report from The Economist: The fuzzy specks growing on discs of jelly in Floyd Romesberg's lab at Scripps Research in La Jolla look much like any other culture of E. coli. But appearances deceive -- for the dna of these bacteria is written in an alphabet that has six chemical letters instead of the usual four. Every other organism on Earth relies on a quartet of genetic bases: a (adenine), c (cytosine), t (thymine) and g (guanine). These fit together in pairs inside a double-stranded dna molecule, a matching t and c, g. But in 2014 Dr Romesberg announced that he had synthesised a new, unnatural, base pair, dubbed x and y, and slipped them into the genome of E. coli as well. Kept supplied with sufficient quantities of X and Y, the new cells faithfully replicated the enhanced DNA -- and, crucially, their descendants continued to do so, too. Since then, Dr Romesberg and his colleagues have been encouraging their new, "semisynthetic" cells to use the expanded alphabet to make proteins that could not previously have existed, and which might have properties that are both novel and useful. Now they think they have found one. In collaboration with a spin-off firm called Synthorx, they hope to create a less toxic and more effective version of a cancer drug called interleukin-2.
Interleukin-2 works by binding to, and stimulating the activity of, immune-system cells called lymphocytes. The receptor it attaches itself to on a lymphocyte's surface is made of three units: alpha, beta and gamma. Immune cells with all three form a strong bond to interleukin-2, and it is this which triggers the toxic effect. If interleukin-2 can be induced to bind only to the beta and gamma units, however, the toxicity goes away. And that, experiments have shown, can be done by attaching polyethylene glycol (PEG) molecules to it. The trick is to make the PEGs stick. This is where the extended genetic alphabet comes in. Using it, Synthorx has created versions of interleukin-2 to which PEGs attach themselves spontaneously in just the right place to stop them linking to the alpha unit. Tested on mice, the modified molecule has exactly the desired anti-tumor effects. Synthorx plans to ask permission for human trials later this year.
Interleukin-2 works by binding to, and stimulating the activity of, immune-system cells called lymphocytes. The receptor it attaches itself to on a lymphocyte's surface is made of three units: alpha, beta and gamma. Immune cells with all three form a strong bond to interleukin-2, and it is this which triggers the toxic effect. If interleukin-2 can be induced to bind only to the beta and gamma units, however, the toxicity goes away. And that, experiments have shown, can be done by attaching polyethylene glycol (PEG) molecules to it. The trick is to make the PEGs stick. This is where the extended genetic alphabet comes in. Using it, Synthorx has created versions of interleukin-2 to which PEGs attach themselves spontaneously in just the right place to stop them linking to the alpha unit. Tested on mice, the modified molecule has exactly the desired anti-tumor effects. Synthorx plans to ask permission for human trials later this year.
next they can work on adding PSI genes for the dogboys
In an unrelated story, 15 foot tall man-eating mice have been discovered in La Jolla.
After the tumor is gone, the patient grows razor sharp talons, gains superhuman strength, and develops an insatiable desire to drink human blood. So that's the downside. But hey, no cancer!
Genetically-improved E. coli.
#DeleteChrome
Seems like some people fail to remember that basic alterations created misfolded proteins that affect mammalian brains, and reactivated otherwise extinct diseases.
Oh well, it was nice to have humans around for a while.
-- Tigger warning: This post may contain tiggers! --
Do you want World War Z?! Because that's how you get World War Z!
Welcome our new 6-letter cure-all overloards!
Some DNA is just more equal than others.
I really don't think a civilization that can't stop actively destroying it's planet should be fooling around with new and interesting DNA base pairs.
Taking the perfection out of our creators work will not make things better.
All the new six pair drugs will also now require two factor authentication.
E.T.'s DNA has six letters too. Move over, humanity.
mark of the beasts ... ...
seeds of the serpent
I guess it's not surprising that millennials never leave home. They can't even find their own shift key.
After dna, a, t, c, and g, Og somehow managed E. coli (more than once, even, though not in italic).
If not for the Donald we might not have had the cure for cancer.
Or you could have 70% taxes u set Pelosi.
A whole bunch of whiners here seem to be worried about this - not one post on super awesome positive human mutations that may occur.
Live it up a little and stop worrying so much!
This is just the kind of thing I would think especially the trans-human community would be super into.
"There is more worth loving than we have strength to love." - Brian Jay Stanley
1: find bases X & Y which cannot be naturally or easily obtained
2: engineer bases X & Y into human germline
3: monopolise production of X & Y
4: wait a few* generations for X & Y dependence to spread throughout the entire population
5: profit or extinction!
I really hope this is happening in an off-world level 5 containment facility.
"The ability to delude yourself may be an important survival tool" - Jane Wagner -
1) Making proteins with unnatural amino acids has been possible and done before.. like a lot of times.
2) Attaching PEG to proteins, a process called pegylation, has been done before and is a routine process.. although it is rather random. Most pharmaceutically used proteins are pegylated, as the attached PEG seems to make them more long-lived/potent. Making it more specific can be done in much much easier way than this (via Cysteines or surface engineered Lys etc., just to name two options).
So now they make highly sophisticated changes to E. coli, create two extra bases, ensure that they translate those two extra bases into the right unnatural amino acids, so that they can make specific PEG-attachments in order to prevent Interleukin-2 from binding the alpha-subunit.. whoa.. have they ever thought of a more convoluted way? Pro-tip: just mutate Interleukin-2 to no longer (or at least weaker) interact with the alpha subunit like here [1] (paper from 2013).
[1] http://www.jimmunol.org/content/jimmunol/early/2013/05/15/jimmunol.1201895.full.pdf
OMG,genetically modified bacteria are gonna kill us!
No. They won't. That's the beauty about this stuff. To be blunt, I'm no big fan of GMO myself, but this is the kind of GMO I could get behind. Why? Because it has a built in kill switch. Those bases X and Y don't exist in the wild. In other words, for your bacteria to live and multiply, you have to keep feeding them these things after artificially creating them. You want your bacteria to die? Just literally starve them to death by not providing X and Y.
This is the kind of therapeutic GMO bacteria that are just perfect. Use them while you need them, then after they've done their job just cut off their supply of food and they're dying. Beautiful.
We used to have a Bill of Rights. Now, with the rights gone, all we have left is the bill.
What they really mean are "human EXPERIMENTS", because mice are nothing like humans (in case you hadn't noticed), and experiments on mice don't predict outcomes in humans. So ALL 'clinical trials' are actually 'human experiments'. And this will FAIL miserably, like all the other magical treatments for cancer have, which allegedly worked in one species of animal or another (we only have the 'researchers'' say that their results are actually true - most landmark cancer studies are not REPLICABLE, which means they were fraudulent in the first place, and have been quoted and used as a base for other research ever since).
This will FAIL and won't work in humans. Remember, you read it here first. You should be skeptical of ALL research that involves vivisection - people who torture animals to death all day are hardly the sort of people you should trust.
OMG,genetically modified bacteria are gonna kill us!
No. They won't. That's the beauty about this stuff. To be blunt, I'm no big fan of GMO myself, but this is the kind of GMO I could get behind. Why? Because it has a built in kill switch. Those bases X and Y don't exist in the wild. In other words, for your bacteria to live and multiply, you have to keep feeding them these things after artificially creating them. You want your bacteria to die? Just literally starve them to death by not providing X and Y.
This is the kind of therapeutic GMO bacteria that are just perfect. Use them while you need them, then after they've done their job just cut off their supply of food and they're dying. Beautiful.
I was reading about this work in New Scientist a few weeks ago, one of the primary objectives of this research is to target pollution, making these self regulating in the way you describe is actually a central tenet of this.
Are they wholly synthetic or naturally occurring but unused?
Nature is not an idiot. And the 4 billion years of evolution made the base pairs what they are. They should be asking why rather vigorously, not tinkering with the way it is presently. If this gets into human germ cells and is passed along from generation to generation along with other "improvements," may we (humans) not some time in the future be forced to say..."ooops, maybe we shouldn't have done that?"
E Proelio Veritas.
Eventually, someone will screw this up, or not to mention the people who will try to actively weaponize this stuff. All of the DNA tinkering just brings up visions of post apocalyptic earth where hideous GMO's feed on the remaining small human population. Not to mention the modified bacteria and viruses that will be attacking our descendants.
Of course, some good science fiction should come out of this, but I am not sure future humans will have time to read while fending off monsters and disease.
Murphy's law is a thing, and eventually you're going to hear a geneticists say oops. We definitely need some very good safety protocols for this.
Nature needed a binary coding system to store information, and she built one. The AG-TC system is robust and works well. Do we really need trinary encoding?
I mean at a technical level, this would permit DNA coding sequences to be shorter... but you'd still need a very long molecule to encode for any reasonable form of life. The physical maintenance needs, the replication infrastructure, all that wouldn't change much.
This strikes me as more of an interesting intellectual exercise. At this point anyway.
I've been mixing KY in my DNA with my wife for years.