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Precision Gene Editing
mpthompson writes "NewScientist.com is reporting that scientists at Sangamo Biosciences have developed a method of editing DNA mutations with unprecedented precision without weaving in potentially harmful foreign genetic material. Different combinations of amino acids are designed to latch on and cut the DNA at exactly the place where the mutated gene lies. This triggers the body's natural repair process which corrects the gene where the DNA was cut. The technique will be used to target diseases caused by single-gene mutations such as combined immune deficiency (X-SCID) - or bubble boy disease - and sickle cell anaemia."
Once you start minipulating genes you're acting as god. Short term good may come of it, but the potential to screw up is an inevitable human trait..If we screw up here, we screw up bad.
OT: Anyone else noticed slashdot's 'free day pass' where u watch an ad then you get a free day of slashdot subscription? The thinkgeek ad was pretty funny.
time is a perception of a being's consciousness
time is your 6th sense, the wierd ones are 7+
Just wondering.
is it just me pr did slashdot add a "daypass" if you watch a commercial to see unreleased stories yet instead of subscribing?
Noone writes jokes in base 13!
The article only mentions cutting the DNA and then "allowing the body's natural repair processes" to do the rest - it seems that this technique could also be useful in inserting genes at precise locations in DNA instead of letting viruses and bacteria insert genetic material wherever they please? I am no genetic engineer, can anyone comment?
So this treatment actually alters the genetic code of a human? So any genetic disease would not get passed down to future generations? How is something like this administered? Our DNA is found in every cell of our body.
--
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With adblock on it was just a matter of clicking a couple times, didn't see the ad. Now I see what I'm missing by not subscribing (hint: nothing).
they say diarrhea is hereditary, it runs in the jeans...
A feeling of having made the same mistake before: Deja Foobar
"and it is among the benefits of science that it equips the future for its duties."
-- Alfred North Whitehead, 1927
I know people who are geneticists, and who work in a lab where they are able to essentially make a mouse to order. You want one that grooms obsessively, here you go! Want one that glows in the dark? You got it. Just because they do it through genetic manipulation rather than breeding doesn't make it any more evil than other means.
What it does do is accelerate our ability to learn about life. Should we take things in measured steps? Absolutely! We should also have been more careful about asbestos, lead based paint, DDT, agent orange and more. But should we ignore these amazing advances? Absolutely not!
The CB App. What's your 20?
Before the first atom bomb was detonated, there were some scientists that thought that the nuclear reaction would spread and ignite the entire atmosphere. Despite their reservations, the tests were done anyway. Screwing up has never been a risk people considered worthy enough to stop a scientific experiment.
Rhymes that keep their secrets will unfold behind the clouds.There upon the rainbow is the answer to a neverending story
I have a feeling that this has to do with homologous recombination, where damage to a certain gene causes the chromosomes to auto-repair themselves by copying the target gene from the "good" chromosome. At least that's my take on why they would mention damaging the DNA to repair it.
I am defenseless. Use your button. Mod me down with all of your hatred.
Great, now the gene splicers have the equivalent of a hex editor, but still have no clue what they are editing. It's like hacking binary code out of one program and inserting into another program and somehow getting it to work.
Until we have a better handle on Gene Expression and how to actually interpret the genetic code we should proceed cautiously.
To quote Dr. J. Craig Venter, Time's Scientist of the year (2000).
"We know far less than one per cent of what will be known about biology, human physiology, and medicine.
My view of biology is 'We dont know shit.' "
If any am being overcautious or am ill-informed please feel free to correct me. I try to live by the motto, "Just because we can do something, doesn't mean we should." This applies to System Administration as much as it does to gene-hacking.
This means the son of the goatse.cx man will not be posing on the Internets.
I think there is a natural equilibrium between nature and gene mutations. When the hand of man starts changing one side of the equation, can the consequences on the otherside be foreseen? For example, who is to say that some form of cancer today won't mutate to something 1,000 years from now that will save humanity from some enviormental change?
Rosco: "If brains were gunpowder, Enos couldn't blow his nose."
http://www.biologynews.net/archives/2005/04/05/res earchers_pioneer_new_gene_therapy_technique_using_ natural_repair_process.html
like the 'bubble boy' defect mentioned in the article, we often know the specific bit of code that causes the problem.
n odeficiency
"IL-7 signalling pathway
Most cases of SCID are derived from mutations in the c chain in the receptors for interleukins IL-2, IL-4, IL-7, IL-9 and IL-15. These interleukins and their receptors form part of the IL-7 signalling pathway.
The IL-2 receptor (IL-2R) gene is located on the X chromosome and mutation of this gene causes X-linked SCID.
Janus kinase-3 (JAK3) is an enzyme that mediates transduction of the c signal. Mutation of its gene also causes SCID."
http://en.wikipedia.org/wiki/Severe_combined_immu
Have fun on your computers tonight! Don't stay up too late playing your Doom 3 or whatever.
TFA noted that the zinc fingers cue in on two sets of 6 base pairs to find the site that needs correction. Assuming randomness in the base-pair sequences, this 12 base-pair key will bind with approximately 1 out of every 16.8 million (actually 1 out of every 8.4 million due to complementarity of the base pairs). Given that the human genome has about 3.2 billion base pairs, this means that the modifier will match in 381 positions more or less.
Thus, this method will fix the error in one place and introduce an error in 380 other locations. The key needs more than 16 base pairs to be statistically assured of homing in on a unique mutation (depending on the statistics of DNA, it may need more or less).
Two wrongs don't make a right, but three lefts do.
I have not read the article, but repair processes can be "error prone". That is, the mechanisms cells use to repair DNA often involve high error rates.
/.ers may not appreciate is that typically, it is VERY, repeat VERY hard to get chemcial reaction specificity of anywhere close to 1e9 for reactions invovling DNA.
The human genome is 3e9 BP long (roughly..not counting indels, the unsequenced centromeres, etc etc)
So the chemical process of identifying the one single mutated basepair has to have a chemical specificity of >>1e9, because there are >>1e6 cells that are exsposed. That is, lets say you feed the reagent to a person. Millions of cells, each with 1e9 bp, are expsosed. Say the process has an error rate of 1e10 - many, many cells will have incorrect repairs done
This is just like error rates in, say, reading data from a harddrive: the larger the file, the lower the error rte has to be
What
I will rtfa,
Really, emacs is a whole lot of stuff that just happens to have text editing functionality along with it, so why not genes?
I note that the process involves removing blood from the body, running the process on cells purified from teh blood, and then reinjecting the cells back intothe patient.
I believe, but am not an expert in this field, that the simple process of removing cells from the body is in and of itself, highly mutagenic.
There is *no way* the cells could be checked before reinjection.
In any event, it is an interesting piece of science, but a LONG way from clinical practice - stay tuned for the update in 2020.
I think you meant the biology news link to the same research
Your original has some extra characters and can't be used.
-- Tigger warning: This post may contain tiggers! --
Pharmacorp executive: "Let's see now, we can sell them a one-time treatment that cures them for the rest of their lives, OR we can charge them $1000/month for drugs to maintain their current status for the rest of their lives... well, obviously we'll choose the method that is best for the patient's well being, our profits be damned! I mean, it's not like we have a board of directors that will sack us if our revenues don't increase every quarter!"
I've abandoned my search for truth; now I'm just looking for some useful delusions.
in 500 years, and between then and now millions of people suffer painful deaths to avoid changing something that might be helpful in the case of your hypothetical event?
Anyway, there is the whole somatic vs. germ line thing, if genetic engineering is limited to somatic cells, changes won't be passed on to children (unless we start reproducing via mitosis).
[obscure Seinfeld reference] The Mooks.
germ line changes.
If a person has a terminal disease, somatic changes may or may not help, but they aren't likely to cause more damage than the disease.
And by the time they have a terminal (or even chronic) disease, you can get a pretty good idea how "the organism will express it's genes".
Treating disease in somatic cells is a much different issue from creating new lines of plants/animals/humans via changing germ line cells--at least in organisms that reproduce sexually.
I am getting real tired seeing all this great research, only to realize that treatments are the same tired treatments at the beginning of the century.
NONE OF THIS RESEARCH has changed people lives.
Stop with the fairy tales. People have not and will not get any new cures to any existing health issues.
our brains allow us to control nature, not just exist in it. We can do whatever want, but we should be responsible when it comes to genetics because it puts our entire species at risk. If a person wants to design their genes let them, but there must be some rules and standards.
Thats why we don't depend on that industry. Buy your drugs in India, take a vacation and come back with your genes fixed.
ThE chhosing
But it does give us the ability to create the equivalent of patch files for bad/defective genes when a good/functional version of the gene is available.
There are many genetic diseases where the mistake in the DNA is well characterized, and it is very clear exactly what difference between the normal version of the gene and the defective version causes the disease, even if we don't have a full understanding of what the hell gene does; we just know to a high degree of certainty that a particular error causes a particular phenotype.
This new technology, if it lives up to the hype it's given here, could mean we can fix these kinds of diseases.
Yikes!!!!
contact to see if corporations the above Is far dabblers. In truth,
My children can finally be bred as Valids!!!
Hello Greg Bear, are you reading this? We need a trilogy. Maybe Darwin's TV. For /.ers -> for reference read Darwin's Radio and Darwin's Children. Much fun and profit in them there genes.
Too lazy to create a sig...
In fact that's exactly what the article says: "This triggers the body's natural repair process, called homologous recombination, which corrects the gene where the DNA was cut, The researchers provided the cells with a copy of the correct gene as a template."
If they were to concentrate this work on Myotonic Muscular Dystrophy, they could likely achieve a success very quickly. It is caused by an unstable CTG sequence of DNA that expands in length when replicated. The progression of the disease is characterized by the number of expansions. Since it is an unstable sequence and of little use, simply cutting it out of all DNA should "cure" the disease. I put the "cure" in quotes because reversing the damage is likely not possible, but it could at least eliminate it from future generations and stop the progression.
Selective breeding in the past did not create the equivalent of a "critical mass". One or two relatively minor mutations across may be tens or hundreds of specimens, then later, more interbreedings to select the characteristics. All the while, nature and time being the moderator allowing the weak, damaged, or DANGEROUS to fail or be isolated in the necessarily small group. Instead, a hurried implementation of mass genetic change could conceivably create a critical mass, such as planting a gene corn throughout the world, and though maybe technically inferior over a long time, but strong enough to survive in the ecosystem and disrupt native species, even though the erosive nature of time and nature would eventually win by selection.
Does ten small, hairless dogs have a chance to propagate in the wilderness?
Does a million? A big difference.
I simply cannot agree that old style breeding == new style en-masse genetic manipulation.
Highly efficient endogenous human gene correction using designed zinc-finger nucleases
FYODOR D. URNOV1, JEFFREY C. MILLER1, YA-LI LEE1, CHRISTIAN M. BEAUSEJOUR1, JEREMY M. ROCK1, SHELDON AUGUSTUS1, ANDREW C. JAMIESON1, MATTHEW H. PORTEUS2, PHILIP D. GREGORY1 & MICHAEL C. HOLMES1
1 Sangamo BioSciences, Inc. Pt. Richmond Tech Center 501, Canal Blvd, Suite A100 Richmond, California 94804, USA
2 Department of Pediatrics and Department of Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, Texas 75390, USA
Correspondence should be addressed to M.C.H. (mholmes@sangamo.com) or M.H.P. (matthew.porteus@UTSouthwestern.edu); requests for materials should be addressed to M.C.H.
Permanent modification of the human genome in vivo is impractical owing to the low frequency of homologous recombination in human cells, a fact that hampers biomedical research and progress towards safe and effective gene therapy. Here we report a general solution using two fundamental biological processes: DNA recognition by C2H2 zinc-finger proteins and homology-directed repair of DNA double-strand breaks. Zinc-finger proteins engineered to recognize a unique chromosomal site can be fused to a nuclease domain, and a double-strand break induced by the resulting zinc-finger nuclease can create specific sequence alterations by stimulating homologous recombination between the chromosome and an extrachromosomal DNA donor. We show that zinc-finger nucleases designed against an X-linked severe combined immune deficiency (SCID) mutation in the IL2Rbold italic gamma gene yielded more than 18% gene-modified human cells without selection. Remarkably, about 7% of the cells acquired the desired genetic modification on both X chromosomes, with cell genotype accurately reflected at the messenger RNA and protein levels. We observe comparably high frequencies in human T cells, raising the possibility of strategies based on zinc-finger nucleases for the treatment of disease.
Most human monogenic disorders remain difficult to treat because therapeutic transgenes do not undergo homologous recombination (HR) into the mutated locus1, 2, and gene addition by virus-driven random integration remains a challenge owing to transgene silencing, improper activity or misintegration3, 4. Furthermore, targeted alteration of DNA sequence in vivo--in principle, a powerful basic research technique for studying genome function--in mammals requires sophisticated targeting vectors and drug-based selection1, 2, which limits the use of this approach5-7.
The C2H2 zinc-finger, originally discovered in Xenopus8, is the most common DNA binding motif in all metazoa9. Each finger recognizes 3-4 base pairs of DNA via a single alpha-helix10, 11, and several fingers can be linked in tandem to recognize a broad spectrum of DNA sequences with high specificity12-14. Engineered zinc-finger protein (ZFP)-based DNA binding domains with novel specificities have been extensively applied in vivo to target various effector domains12, 15. Work from the Chandrasegaran laboratory has shown that a ZFP can be coupled to the nonspecific DNA cleavage domain of the Type IIS restriction enzyme, FokI, to produce a zinc-finger nuclease (ZFN)16, which then cuts the DNA sequence determined by the ZFP16, 17. An important specificity mechanism derives from the requirement that two ZFNs bind the same locus, in a precise orientation and spacing relative to each other, to create a double-strand break (DSB; Fig. 1a)17. One mechanism by which eukaryotic cells heal DSBs is homology-directed repair (Fig. 1b)18-20, which transfers information missing at the break from a homologous DNA molecule (Fig. 1b). Work from the Jasin laboratory21, followed by that of others22, 23, demonstrated that the endonuclease I-SceI can potentiate HR into loci previously engineered to contain its own recognition site, and the Carroll24, 25 and Baltimore26 laboratories have shown that a ZFN-invoked DSB increases the rate of HR in model systems.
Figure
In this case, the Zinc Finger Nuclease is simply used to cut the defective DNA to initiate the homologous recombination process. If you had bothered to read the abstract you would understand that they are also providing an "an extrachromosomal DNA donor" (I would suspect on a plasmid) as the source for the corrected DNA sequence.
So this process *need not* be error prone. Of course they are obviously looking at a number of cells after the fact to determine the fraction of cells in which the process was successful. If one did this with stem cells (which seems to be where they are going) and put them back into the body then one would indeed be able to correct SCID or sickle cell anemia. Diseases that are present in adults in specific cell types such as cystic fibrosis or muscular dystrophy are going to be a bit trickier.
To have a technique that could possily cure people and then not use it for "religious" or for whatever fear is to my mind immoral - we may as well be living in the dark ages. Obviously the technique needs work still, and there are always risks with any medical procedure. Provided the patient knows fully those risks and agrees I don't see a problem, particuarly when no harm to anyone else is being done. The technique isn't introducing any alien material into a human. AND in any case we are already mutated by dioxin and radiation and any number of chemicals eg PCB's etc. in the environment. So how is this technique going to change the face of being human? And to those who have made fun of the illness, I suggest that you fully investigate the illness and the suffering it causes thousands of people every day. There are {at current tally} at least 85 variations of Primary Immune Deficiency - X-linked SCID being only one of them. The technique mentioned will only cure one variation anyway. Not the other 84. Still it is worth pursuing as more knowlege is another link in the chain eliminated. Check out; http://www.jmfworld.com/ http://www.pia.org.uk/