A new "find-and-replace" genome editing method enables scientists to make large-scale changes to the genetic code of a living cell, faster than previous editing technology by a factor of two. The new method could be used to engineer cells that produce new proteins, or to design genetic "firewalls" that would prevent engineered cells from spreading their DNA.
Using a new genome engineering method, researchers from Harvard University and MIT were able to systematically replace one three-letter DNA "word," or codon, with another one, throughout the entire genome. Their method reimagines genomes as editable templates, allowing entire sections to be rewritten without interrupting the overall organizational structure.
Ever since genome sequences were unraveled, scientists have been experimenting with ways to edit them, to give cells new capabilities and to cure diseases. But progress has been slow, in part because the editing job must be incredibly precise — one misplaced allele on a chromosome can be lethal. Introducing individual changes is therefore laborious and difficult.
Genetic scissors like zinc-finger nucleases can do the job, glomming on to certain sequences of a genome and cutting it out. Engineered viruses can then bring new DNA to the targeted area. Just last month, researchers successfully snipped out the genes that cause hemophilia, in a study involving living mice.
Rather than using scissors, this new method is akin to the find-and-replace function on your word processor, seeking out individual codons and replacing all of them with something new. The researchers used E. coli bacteria and edited a codon that only appears 314 times in the genome, spelled TAG.
Most codons spell out the sequence of an amino acid, as a Harvard Medical School news release explains. But some codons direct a cell to stop adding amino acids to a protein chain. TAG is one such stop codon, and it happens to be the rarest word in the E. coli genome. The team used a method called multiplex automated genome engineering, or MAGE, to replace the TAG codon with another stop codon, TAA.
MAGE locates specific DNA sequences and replaces them with a new sequence as the cell copies its DNA. The team made 32 E. coli strains, each of which had 10 TAG codons replaced. Then they used a new technique called conjugative assembly genome engineering (CAGE), which allowed them to control the process that bacteria use to swap genetic material.
The researchers believe they're on track to replace all 314 of them — without harming the cells in any way.
The next step would be to take out the genetic sequences that allow the cell to read the TAG stop instructions. This machinery could then be used for an entirely new purpose, like encoding a new protein or function.
The research is described in today's issue of the journal Science.
Wow.. Doubling the outcome speed is a pretty damn large step forward, it also means that any discovery is going to be made twice as fast. For each step towards curing aliments, we need to take a step or two towards food production, or we'll be left with far too many mouths and not enough food. Natural Selection worked for a reason, man as continued to find better and better ways to circumvent it...
Playing Devil's Advocate since 1978
"The only constant in the universe is change"
-Heraclitus of Ephesus 535 BC - 475 BC
I know no one will believe this, but as a biomedical engineering major, I had the idea to use zinc-finger nucleases to do this kind of cut-and-replace function to DNA before I even knew what zinc-finger nucleases were. At the time, I imagined a "programmable artificial restriction enzyme" that would target sequences and cut them out. Then, using a delivery method as-yet-unknown (I didn't think of viruses, I'll give them that) you'd deliver the modified pieces of DNA and have ligase reattach them to fill the new gaps.
It's exactly what they're doing. Scientists have already cured mouse hemophilia with this, which is great, but I had come up with the idea to use it for cancer treatment. All cancer is, at its very roots, a genetic mutation that destroys the cell cycle. Fix the mutation, you fix the cancer. Being able to target the mutant cell and "find-and-replace" it with healthy DNA is the perfect cure for cancer. Let's hope a real scientist thinks of this as well.
-IMP ;) :)
One of the incredibly appealing aspects of this is that beause it's done by means of e. coli wouldn't it be possible to change an entire organism by means of an infection? This seems like it could be used to insert a triggered kill code in all your cells so when a cell becomes cancerous it would immediately die. likewise we could replace and repair all DNA we wanted to change. If it actually works the way i've speculated we are well on our way to immortality.
@ Nadure Baile:
This experiment was done to the E. coli genome. E. coli cannot alter another organism's genome by the same process. Not only that, but it is much easier to carry out this experiment with E. coli in a test tube than it is to target, for example, cancer cells in a living human. This might be the beginning of the ability to change human DNA at will, but its still a long ways off.
darn...now i feel really stupid.... oh well
"seeking out individual codons and replacing all of them with something new"
Definitely good to hear about improvements, but how is a bulk search and replace good?
Due to my limited knowledge in this area, it appears to me a flawed way to trying to make & test changes.
If 1 sequence represents some property, I doubt that same sequence in another location would represent the same thing.
Unless there is a lot of redundancy
Basically, this looks no different to me than hex editing code and never once has a bulk find & replace of a hex sequence ever worked. It usually breaks the app.
For example, I would not change all spots where I find a sequence like "F2AB".
In one spot, it may increase the number of lives in a game or remove a CD check....but changing all spots that it appears in would kill functionality and make the app crash.
Its pretty interesting though that genetic engineers are just hackers that are "accepted" in society.. even though they could potentially cause more damage than any hacker could.
This is SO freaking cool, it's almost like computer programming just on a much grander scale! I would definitely love to see where this takes off in the future. I myself am heading into the computer field but have always held a fascination with biology. Very exciting stuff indeed! :)
So about the sequence replace, dna represents proteins, using stop blocks to indicate the end of a protein means that if that protein is found in place A and place B the protein created is always going to be the same per the same sequence. What parts of the DNA is active as per the given cell a bad protein may exist in a few places. It is not the same as software development, (Function calls are in line). So this would be like changing an in line function and every place that references the function will be updated once compiled.
It's not only twice as quick, but from what I read this technique only costs around $90,000, compared to a similar technique pioneered at the Venter Institute last year that cost about $40 million.
While this specific method can really only be used with bacteria, there are huge amounts of bacteria living in the human body. If we could re-engineer those bacteria to be more beneficial to us, using approaches such as this, then this could produce major benefits.
Just as one example, it might be theoretically possible to engineer bacteria in the human gut to be able to digest cellulose fibers, like termites do, meaning that we could get more nutrition out of our food. Therefore, this might actually lead to a step forward in food production, as one of the previous commenters urged.
I believe this was proof of concept rather than proof of any specific application for the process, although they must have plenty of ideas on how this process might be applied.
And yes, they are a bit like "hackers". However, not all hackers are bad. Many companies and government agencies hire hackers to break into their systems. They then report on the overall state of security and make recommendations on how better to secure these systems.
This is no different. The science is what it is. Individuals will use it for various reasons, some good and some bad.
Humanity @ it's best
Heee I don't see a UNDO button!!!! because surely somewhere in these sequence of words it will spell DOOM!!! yes I know you only see ACGT, but with a little bit of imagination you're able 2 read ACGT as DOOM.