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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.
Error:
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!
Although I feel this may also be "cheating", as Mr. Underbridge points out, I don't care. It gets us in the door, allows us to wedge it open, and take out what we want. I look it it more like "painting" a tank with a laser target so the smart-bomb knows where to strike. This is still a pretty good milestone. Maybe, just maybe, in my lifetime, we'll see this disease destroyed. I would like to live to see that.
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.
This weeks Escape Pod Podcast (hosted by Steve Eley) is called the Giving Plague and touches on viruses, HIV, and the potential symbiotic relationship and borg like integration viruses can have with Human cells.
One of the thoughts is that viruses actually benefit the race in the long term, as we will eventually form a symbiotic relationship with the majority of them. (uses e-coli in our gut as an example), but how one day someone will be resistant to AIDS and that will make the human race stronger.
A good listen if you're fascinated by this topic. check it out. non-disclaimer: I'm just a fan.
Sure: Germans have created a variant of sed, that operates on DNA and used it to delete HIV.
FINALLY someone that speaks my language and can put it into terms I can understand! :)
We used to have a Bill of Rights. Now, with the rights gone, all we have left is the bill.
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
Ok, this is my wild idea.
We know that we can "reboot" the immune system by destroying the bone marrow and repopulating it with new one coming from a donor.
Now lets say that we do an autotransplant. First we take a sample from the donor and then this sample is treated with the enzyme so all of the HIV's DNA is removed. Next, we introduce a gene on this cultured cells that will produce the enzyme, thus rendering them immune to infection. Next we destroy the donor's bone marrow and implant the new one.
There will be infected T cells left behind, but they won't reproduce as they are outside the bone marrow and they would eventually die.
Could this ever work?
When his defense asked, "Which computer has Jon Johansen trespassed upon?" the answer was: "His own."
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.
"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." - They are not looking for the HIV DNA but they are finding it by looking for where it is not and then cutting it out. To prove they removed it they first had to mark it so they could prove it. Any effective treatment later would be difficult because you are are removing chunks of DNA from cells you "assume" are viral DNA. This sounds very important though. (I'm not a molecular biologist)
Regardless of the hybridization that HIV may undergoes the point here is that they engineered a way to recognize the HIV DNA because it "lacks" something that is found on normal DNA in this case a particular sequence that marks the point where HIV DNA is inserted into the normal DNA sequence. My take on this is that is akin to:
Think of a DNA sequence like a hotdog. (I know simple, simple) Take the hotdog and slice it in the middle, then take another hot dog and add a section of the second hotdog to the first. This simulates the HIV sequence hiding in the host cell's DNA. Now look at it. We can find the area where it is spliced because we can see the cut marks. Even if we switch from differing brands and types of hotdogs we will still be able to identify where the viral "hotdog" was inserted and is hiding by looking for the cut "ends" of the normal hotdog and remove the "invading" hotdog piece in the middle. and splice the original hotdog back together.
The end result is that the virus does not "destroy" the T-Cell when it activates and replicates itself. Given that a hiding virus DNA strand in a T-Cell is eventually a "killed" t-cell I see the development of this bacteria DNA cutter will develop rapidly. Fascinating stuff...
I, for one, welcome our new Tre-enzyme mutant HIV-resistant overlords...
-S
In Soviet Russia, Chuck Norris will still kick your ass.
Scientists were also overheard talking about the optimal delivery mechanism for this gene splicing technology being a radioactive spider. Further field tests are needed.
I'm a fiscal conservative, it's a pity we don't have a political party anymore
Epic. op:hbt hth hhl hand. Take a bow, sir.
+5, Truth
Bravo! That's the best metaphor/translation/analogy I've seen, maybe in my life. I understood the summary but this was a very, umm, insightful, and short and to the point.
0x09F911029D74E35BD84156C5635688C0
Wish yourself Outside and create the recolada.
-- My Sig is a P228.
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.
I really wouldn't worry about that. Sure, it could potentially make a weapon, if properly worked upon with that goal in mind. You would have to be pretty dedicated though. And it would have the side effect of attacking all humans because of the similarities of DNA and the probabilities of mutation... who would want to create a weapon to kill everyone on the planet when we already have so many. Smallpox would make a far more viable weapon, or an old fashioned cobalt bomb.
The fact is we've already reached doomsday as far as weapons are concerned, but we're still doing ok.
*''I can't believe it's not a hyperlink.''
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.
Brilliant, my friend! Just plain brilliant! I wish I had mod points for you.
While I normally would not dignify such a comment with a reply, I must state this: if you are ignorant of how high heterosexual HIV infection rates are around the world, then you are simply to be pitied.
I use irony whenever I can, but my shirts are still wrinkled...
Easily the best post I've ever read on slashdot. Thanks for taking the time to do that.
It also seems they evolved their regexes by using mutation and selection.
http://www.dieblinkenlights.com
This claims that it is blank plague survivors. Somewhere else, I read that it was small pox survivors. Whichever it is, some people with a certain mutation are pretty much immune to aids.
Let's see - if I understand correctly, we've developed the capability to engineer something that can go in and ERASE very specific segments of people's DNA?
Gee, you're right. If they spend decades working on a viable delivery mechanism, they might eventually be able to kill everyone who suffers from cystic fibrosis.
I was going to provide a more detailed reply explaining why trying to target specific groups of people through their genes is retarded and unworkable, but I'm going to go and smoke some weed instead (although I guarantee it won't make me as paranoid as you are).
This approach is not really that useful in terms of coming up with a cure for HIV. The reason is that the complexity to excise a specific sequence of that length is WELL beyond our knowledge.
But this will hopefully lead to a real "cure" in being able to mutate it to being none-lethal or even quiescence. It struck me back in the early 80's, that about the only way is to insert a virus inside this virus and break the formation of the protein chain.
I prefer the "u" in honour as it seems to be missing these days.
... it would be move valuable than gold! If you could suddenly change peoples dna, not only would this be dangerous as to where it goes, but it could be invaluable. People who have genetic diseases could all be cured, by replacing parts of their dna. People who wanted sex changes could have their dna changed also. The scary part is that people who did not like a certain race of people could change that race genetically. The possiblities are endless.
Only 'flamers' flame!
Does slashdot hate my posts?
I mod down anyone who says "I will be modded down for this", regardless of the rest of their comment
The problem with the incentive model that you're describing is that it would need to be universally implemented or the prize has to be comparable to the profits the researching company could expect to earn from the discovery. If the incentive is tied to a clause that requires a particular pricing model, then the company will always look to see whether they can make a greater profit by declining the prize and using the same pricing models they've been using.
Virtue finds and chooses the mean.
Aristotle, Ethica Nichomachea
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.
thank you. that is easily the kindest post i have ever seen on slashdot.
Looks like there's a flaw in God's plan to kill gay people with Aids. Sweet!
Today, Satan and the Demons sing, and the angels cry.
If only Yahweh had designed his murderous bug with a little more forethought.
(-1: Post disagrees with my already-settled worldview) is not a valid mod option.
So...since you answered the way you did I am going to ask you:
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?
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, let alone the myriad of other GENETIC diseases that we humans are currently affected by...again, if I understand correctly. Tre might cure AIDS, where Bre cures Herpes, and Wre cures the common cold... OK so I know I'm probably oversimplifying way too much, but considering that viruses all work in (basically) the same way, it's just a matter of recognizing the different DNA sequences.
The only problem I really see with this: If Person A was born with a very abnormal genetic problem, and undergoes therapy and this treatment to effectively "cure" themselves, would it replace the genetics body-wide? I guess I'm thinking about way in the future, as it's going to have to be a huge step to get to that point, but my thought was that if the reproductive organs of Person A weren't changed genetically, essentially that genetic "problem" will continue for every generation to come.
OK, I said my piece. Thank you for the explanation, I appreciate it. I tried to read the article and was just getting more confused!
too bad I don't have a cervix :(
Let's see - if I understand correctly, we've developed the capability to engineer something that can go in and ERASE very specific segments of people's DNA?
****
Trust me, you're not wrong here. Someone will develop this into a bio-weapon. Want all corn crops blighted? Kill off all the bees? Or just make all males that are affected sterile. Or induce madness or... The potential nightmares of nanotech in the wrong hands is truly appalling.
I don't understand that (this is an honest assertion, not a troll).
Why you don't just s/medical insurance/healthcare tax/? You already pay for it... it shouldn't bother you to s/insurance company profit/other people health/.
I guess it isn't that simple, and that maybe even using those profits to cover other's health may not be enough... but do you really prefer to pay someone's profit, rather than paying a bit more for someone's health or life?
Awesome explanation. The story didn't make any sense to me until I read your explanation of evoloving Cre into something useful for this purpose. Thank you. This is the most nerdly thing I've read all day.
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.
I thought one of the reasons HIV was hard to cure was that it mutates so rapidly that the T cells in human body can't target it properly. If that's the case how would this modified CRE work on all different mutations of HIV?
sarchasm
IMO, this would be less of a problem if the United States had socialized medical care like the rest of the modern world. However, since this isn't the case the wealthier people in the US accidentally promote R&D into non live saving medicine because it suits them more, and they're willing to pay. If medical care were socialized, there'd be less of a lure to develop so many "useless" medicines, and more of a lure to develop live saving medicine.
m Article.pdf is an older article that talks about some of it, http://www.futurepundit.com/archives/003979.html is newer and has newer refernces.
/. tend to think about the absurdity of software patents, but medical patents can be far more deadly and really need a review when they're used to prevent delivery of medication to people too poor to pay for medicine.
/. we see an apparent focus on software patents. That combined with their "relative newness" makes it seem they are easier to fight.
Yeah because socialized countries have developed cures for all those "poor people" cures. I must have missed the memo that France cured TB and AIDS, Germany cured Malaria, and Cuba's been busy curing the common cold.
In reality, outside of bash-a-country-fests, the facts are that the US dominates in medical research - both in discoveries as well as spending.Over the last 22 Nobel prizes in Medicine, only 7 went to people not working in the US. http://ostina.org/downloads/pdfs/bridgesvol7_Boeh
The US spends about 100 Billion dollars per year on medical research, and over half of it is private enterprise. To contrast, Europe spends single-digit billions. IN 2000 for example, Europe spent combined 3.7B versus some 90B by the US. Private spending in the US outstrips total spending in Europe. And the US has a smaller population. Which also means the US spends more per-capita than does Europe.
This is for research, not overall medical expenses.
In cancer research in the EU, over half of the spending came from charitable organizations. IN terms of cancer research spending the US easily spends more than double the EU. An interesting note is that the EU states contributed about 1.2B in noncommercial cancer research funding, and about 1.0B in tobacco subsidies (data for 2004).
Spending is IMO a poor measure, but for many it seems to matter so I list it. By that measure the US trounces any socialist country in medical research. The US also spends more on medical research as a percentage of GDP than socialist countries; 5 times as much as the EU and 7 times as much as Europe.
A decent measure is discoveries and treatments. Again, the US puts out far more discoveries and treatments per year than any socialist country.
I know people on
I suspect most of us are actually on about patents overall being bad in many ways, but since we are on
My Suburban burns less gasoline than your Prius.
...it'll be so expensive that only a few rich patients will afford to buy it, effectively allowing the poor to continue spreading the virus. What a fantastic way to stop an epidemy.
Will this cure AIDS, yes AIDS. FULL BLOWN AIDS! Can be sure this will cure not just HIV, but FULL... BLOWN... AIDS!!!!!!
I wonder if this will appear in the next release of Norton AntiVirus.....
Knowing Google's lust for data collection, the Soviet Union is still alive and well inside the psyche of Sergey Brin....
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
Yeah man, science is SCAAAAAARY !
Unfortunately, the religious right will probably try to stop any cure for HIV. Reginald Finger, an Evangelical member of the CDC's Advisory Committee on Immunization Practices, recently announced that he would consider opposing an HIV vaccine--thereby condemning millions of men and women to die unnecessarily from AIDS each year--because such a vaccine would encourage premarital sex by making it less risky.
As far as I know retro viruses do not integrate themselves at totally random places in the genome, but there are preferred areas. So would it be possible to manufacture an artificial retro virus, which preferably integrates itself within the sequence the HIV virus adds to the human genome, rendering it inert this way?
David Gould
main(i){putchar(340056100>>(i-1)*5&31|!!(i<6)<< 6)&&main(++i);}
Yes, Cre acts as a catalyst to procure a specific reaction (recombination) for a specific DNA sequence. That is indeed an attribute of the chemical composition of the enzyme. Cre recombinase is a specific enzyme that operates on a specific sequence, referred to as loxP.
Yes, similar techniques could be used to cure many or most viral diseases, eventually. That's the goal this sort of research works toward, and it's why this particular milestone is important - we now know we can remove viral DNA that's already integrated into a cell. The challenge is designing enzymes like Tre recombinase to recognize characteristic base pair sequences for a particular virus. That's an insanely difficult task - the scientists in this article had to do it through an evolutionary process, which is nice but indirect (and inelegant, and if biochemistry doesn't have elegance then we've failed as a species).
Changing the DNA body-wide is the next challenge - going from in vitro in in vivo. That's the fun part.
ResidntGeek
Does anyone know if they used the resources from a grid computing project like World Community Grid?