Slashdot Mirror
Integrated HIV Successfully Cut Out of Human Genome
Chris writes "German scientists have succeeded in snipping HIV out of human cells after it has integrated itself into a patient's DNA. The procedure is a breakthrough in bio-technology and fuels hope of a cure for AIDS. The group is only cautiously optimistic, though, as treating a full-on infection would be substantially different than succeeding in a controlled lab environment. 'Researchers ... began with the bacterial enzyme Cre recombinase, which exchanges any two pieces of DNA flanked on either end by a certain pattern of nucleotides (DNA subunits) known as loxP. HIV does not naturally contain loxP sites, so the team created a hybrid of the two DNA molecules, which they used to select a series of mutated Cre enzymes that were increasingly able to recognize the combined DNA. The final enzyme, Tre, removed all traces of HIV from cultured human cervical cells after about three months, the researchers report online today in Science.'"
Alright, I must be crazy. I was just thinking about HIV in the shower, and a similar idea came to my mind. Now it wasn't identical-that would have been freaky-but similar enough to make my hair stand up when I read the first /. entry this morning
They are about 26 different stains of HIV. Article didn't mention it but I am curious if each strain might require a different technique or if this is strain independent? Either way pretty cool stuff.
Did they do it with an iPhone?
They used the transporter and the pattern from when the person beamed down on the away mission...
I read about this in PhysOrg yesterday and they speak more about something the last paragraph of Scientific American only mentions. The fact that they wouldn't use this enzyme to remove HIV infections but instead to figure out which cells have been infected. The biggest problem in treating HIV is that it can go dormant and undetected for so long during which the host can infect others. It sounds horrible, but even being able to destroy all the cells infected with the virus is worth something though it may often prove fatal to the host. I don't think this is a 'cure' or 'vaccine' merely something that makes HIV treatments much much more effective.
My work here is dung.
HIV does not naturally contain loxP sites, so the team created a hybrid of the two DNA molecules, which they used to select a series of mutated Cre enzymes that were increasingly able to recognize the combined DNA.
So...this technique won't work at all in the real world. It won't even work with actual HIV even in the lab.
It's interesting research for its own sake, but in this case it has absolutely nothing to do with HIV. They simply found an interesting way to remove an arbitrary snippet of DNA. In fact, to make it work with HIV, they had to cheat and add tags to the HIV sequence.
This is like saying I could break into a bank vault after I replaced the lock with one I knew the combination to. It says nothing about the bank, only that I possess the capability to manipulate locks.
Think of this as an initial proof-of-concept. Fiddling with DNA is extremely useful - correcting genetic diseases and curing all sorts of viruses that hang out in your cells comes to mind (e.g. herpes). You could even look at curing cancer, since that's typically due to genetic mutations that could be potentially removed, making cells non-cancerous again.
Eventually, you'll want to be able to recognize and remove longer strands of DNA. I'd also worry about the efficiency - randomly removing strands of DNA from healthy cells is a good way to cause big problems. Existing gene therapies that use viruses to deliver the payload sometimes go astray and cause cancer, which is no good.
Translation: RTFA.
I read the first part of the article and it sounds like a pretty complex process. I don't think the summary is bad, just technical.
This game will waste your life. Don't clicky!
Cre is an bacterial enzyme (a member of a family of enzymes called site specific recombinases) commonly used by researchers attempting genetic manipulations of dna. The cre enzyme recgonises a specific dna sequence (called LoxP sites) just over 30 letters (base pair) long and then catalyses a reaction which can either cut out dna, insert dna or reverse the orientation of dna flanked by loxp sites (precisely what the cre enzyme will do depends upon the number of sites and the order and orientation of the sites). The HIV virus does not contain LoxP sites so these guys "evolved" the cre enzyme by a selective process to recognise DNA sequences that were initially a hybrid of a part of the HIV virus sequence and the cre Loxp site. they continues this evolution until a modified Cre enzyme (now called Tre) could actually recognise the original HIV dna sequence. They then used this Tre enzyme to cut out the HIV virus dna that had inserted itself into the cell genomic dna, freeing the cells of the HIV virus. This is a pretty interesting article, however, as the authors state this is preliminary work. One problem i can envision stems from the fact that HIV virus often inserts itself numerous times into the host genome. When researchers are using cre they have to be careful about the number of copies of the Loxp site in the genome or it is possible for the cre enzyme to cause large deletions of genomic dna or even cause translocations (when the genomic dna found on one chromosome is erroneously attached to that of another chromosome). Such changes to the dna can be highly deleterious to the cell and initiate cancerous changes. hope this helps.
Bleh, TFS sounded like the virus/mutation conversation from Bladerunner to me.
This is a big deal because it shows that this technique which has been used for years to cut out fragments of the genome for replication (via PCR and other methods) could be used to remove the viral elements from a genome. It's a big deal research-wise, but the major problem that will hinder this application from practical application is that HIV hybridizes EXTREMELY fast. Using an artificial bacterial enzyme to remove dna fragments requires a specific nucleotide sequence that it targets. Since HIV "changes appearance" (it actually mutates) at a super accelerated rate (100,000+ faster than animal genome) it makes treating (in this case removing) the virus very difficult. This is the same reason that current HIV treatments are effective at first, but slowly become less and less effective as the virus hybridizes. I'm not sure about needing a different enzyme for every strain of HIV, but that certainly makes sense. I don't claim to be an expert on this topic, but I certainly find it interesting. Just my 2 cents...
Could this lead to people getting away with murder because they can alter their DNA ?
Could this lead to people being framed for murder due to spoofed DNA ?
This sounds like it could destroy the credibility of DNA evidence for high-profile cases in the future.
Wanna fight ? Bend over, stick your head up your ass, and fight for air.
Sure: Germans have created a variant of sed, that operates on DNA and used it to delete HIV.
It has one serious side effect, it temporarily turns you into a rabbi.
It is by the juice of the coffee bean that thoughts acquire speed, the teeth acquire stains. The stains become a warning
They've done it in vitro in a lab. Which is a good start, but that doesn't mean you can now safely screw anything that walks.
They probably haven't developed anything which they could conceivably be administered to a living organism yet - let alone tried administering it to one. Then you've got a battery of tests to make sure it's safe and effective - there's probably at least another 10 years before this could really be a treatment.
The great majority of potential treatments never make it through that development/testing process.
In Soviet Russia, Chuck Norris will still kick your ass.
This idea is based on a widely disseminated misconception, that T-cells don't reproduce when out of bone marrow. They do, and happily so, after being activated by other cells, antigens, cytokines and a bunch of other means.
Your method has been tried, in a way. A patient's blood was essentially flushed with healthy blood from donors, so his whole blood was exchanged. It did no good in the long term, because the HIV infects also macrophages in other tissues than blood. The next wave of the infection came from those macrophages.
Ni.
Sox2 explained it pretty well, I'll try to dumb it down even more. Certain enzymes recognize patterns on DNA, and chop them right at that location. HIV is a virus that inserts itself into your DNA (unlike most viruses, which just use your cells resources to reproduce). The scientists evolved an enzyme that recognizes the sites on either side of the HIV, chops them up, and splices them back together--effectively removing the HIV. The reason it's "preliminary work" and not a magical cure is because the 'patterns' recognized by the enzymes (and the enzymes themselves) were morphed into "fake" sites. In actuality, it's much harder to create enzymes that recognize the actual patterns of the HIV. In addition, these enzymes might find patterns elsewhere in DNA and accidentally chop up your DNA in the wrong locations, removing important parts of your DNA.
Well then all we need to do is write a simple script to iterate over all of the cells in the body and run the sed command. The list may be too long though, so we might have to use xargs, but that's no big deal.
I always knew shell scripting would save lives one day.
One would assume that there are a few critical sequences in the virus, without which it would not function or evolve around. Could the structure of its protein shell be corrupted to cause it to immediately fall apart, a la penicillin? Could changes be made to ensure that it would remain forever dormant?
It would seem that, with this technique, a little sabotage might get nearly the same benefit as cleaning it all out, for much less effort and risk.
beckerist
What exactly is this "Tre" then? I see it's an enzyme, but I guess I'm still a bit confused. Cre acted as a catalyst to procure a specific reaction for a specific DNA sequence? Is that an attribute of the chemical composition of the enzyme, or, well...I guess I really don't understand where that came from. Is it a specific enzyme, or is "Cre" the name attributed to ANY enzyme that acts in this way?
Tre is simply their name for the "evolved" Cre enzyme. Cre is a one of many site specific recombinases/integrases. others include FlpE and PhiC31. they each have specific dna sequences that they recognise and most are derived from bateriophages (a kind of virus that infects bacteria). the bacteriophages use these enzymes to insert dna into the genome of the bacteria that they infect.
OK, so with that, what is Tre? The same type of enzyme with a different chemical composition? The reason I'm asking this is because, if I'm interpreting this correctly, this could have very far reaching ramifications! I can imagine this (enzyme? process?) being used to cure just about ANY virus infection....
These enzymes are encoded by proteins. they made alterations to the amino acids coding for the cre protein and then selected for modifications which could cut the HIV coding sequence as well. in theory, yes the process could be used to generate enzymes which can recognise dna sequences coding for a whole range of viruses but as usual life is not that simple. for a start delivering the enzyme to all the infected cells is a huge challenge. secondly, you would have to be pretty certain that the enzyme recognised with extremely high fidelity the sequence that you wished to cut out or you would end up chopping chunks out of the host genome at random (many of these enzymes have what are called psuedo recognition sites cattered around the genome of most mammals - phiC31 is particularly bad for this.
Lux
But I have to say that I disagree about needing to be careful about the number of infections in the host cell. HIV infects differentiated cells that do not naturally reproduce, so mutagenesis leading to cancer is unlikely, and killing infected cells is very nearly as useful as curing them. The body can/will always make more.
you are correct that hiv is very good at infecting non dividing cells (for this reason viruses based on hiv are used routinely by researchers to infect a range of cells, both dividing and non-dividing). however the translocations which I mentioned earlier are capable of generating oncogenes (essentially cancer initiating genes) by bringing a gene on one chromosome next to a gene on another chromosome to form a fusion of the pair. the philadelphia chromosome present in some leukemias is a good example of this (BCR-ABL gene). such translocations appear to be able to initiate proliferation in non-dividing cells