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Precision Gene Editing
Posted by
Zonk
on Fri Apr 08, 2005 06:37 PM
from the i'd-like-some-gills-please dept.
from the i'd-like-some-gills-please dept.
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."
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Precision genetic engineering? (Score:4, Interesting)
Homologous Recombination (Score:3, Interesting)
Re:Precision genetic engineering? (Score:2)
Re:Precision genetic engineering? (Score:2)
No way. Anyone knows anything knows this will really result in a crazy mutation. Maybe they could play with the part of my genome that doesn't let me create fireballs in the palm of my hand and the body will "fix" it so I can?
Flying would be cool too.
Clarification (Score:3, Interesting)
--
Fairfax Underground: Fairfax County message board and public records [fairfaxunderground.com]
Re:Clarification (Score:2)
Re:Clarification (Score:2)
Re:Clarification (Score:2)
Re:Clarification (Score:2, Informative)
The old technology involves the use of a retrovirus containing the correct copy of the X chromosome gene involved. This copy inserts itself (nearly randomly) into the DNA. The problem with this was that you couldn't control the point of insertion, causing a whole new set of diseases.
The new technology involves repairing the endogenous gene sequence rather than inserting a good copy at another locus
Re:Clarification (Score:3, Informative)
In order to answer your question, i'm going to have to give a little background...
contrary to popular belief, 99.99% of the body's cells don't keep dividing. The somatic cells of the body are replenished by stem cells and progenitor cells which act as the main copy from which all the "backup" cells are made. These cells specialize into skin cells, blood cells, and possibly nerve cells. The only way to have a permanent effect with this treatment would be to fix the mutation in the stem cells/progenitor ce
Re:Clarification (Score:2)
The method used can vary by treatment, but in many cases, a virus is used.
I'm Safe.. (Score:4, Funny)
they say diarrhea is hereditary, it runs in the jeans...
Re:I'm Safe.. (Score:2)
PGGP Generated Gene Protection.
Precise Gene Editing = Hex Editor (Score:5, Interesting)
Until we have a better handle on Gene Expression [wikipedia.org] 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.
In the case of specific genetic diseases (Score:3, Informative)
"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 mediate
Re:In the case of specific genetic diseases (Score:3, Interesting)
"Genes exist in networks, interactive networks which have a logic of their own. The [gene] technology point of view does not deal with these networks. It simply addresses genes in isolation. But genes do not exist in isolation. And the fact that the [biotech] industry folks don't deal with these networks is what makes their science incomplete and dangerous."
Dr. Richard Strohman, Professor Emeritus
Sounds like Strohman is talking about (Score:2)
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.
Re:Precise Gene Editing = Hex Editor (Score:3, Funny)
Razor 1911 brings you the penis extension hack.
Sequence cracked by: PhARAOh
GREETZ to MadKillas, Beowulf, Syxus, Toast, Trilithium.
Re:Precise Gene Editing = Hex Editor (Score:3, Informative)
This isn't entirely true. We can figure out where a gene starts in DNA, and we know how to read the DNA into a protein. We know that from the start point, DNA is broken up into 3's such that each set of three DNA bases code for one amino acid. To use the case of sickle cell anemi
Precise Gene Editing = Patch Files (Score:3, Informative)
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 th
Mutations... (Score:4, Insightful)
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?
What if we get hit by an asteroid (Score:2)
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).
Re:Mutations... (Score:2, Insightful)
To answer your question, think of sickle-cell anemia. One copy of the gene, and you're resistant to malaria (but not immune, i.e. it sim
Not specific enough for safety (yet) (Score:4, Informative)
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).
with a PhD in Genetic engineering (Score:5, Informative)
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,
Re:with a PhD in Genetic engineering (Score:3, Interesting)
And their current results of the 18% corrected rate, as they point out, is therapeutically effective.
Plus, their recognition system using zinc fingers may have a higher recognition rate for the targeted sequence, and the corrections are applied to only a small area of DNA - so the overall error rate of DNA replication/repair is spr
When does the emacs module come out? (Score:2)
Good luck getting medical industry to fund this (Score:3, Insightful)
Myotonic Muscular Dystrophy cure (Score:3, Informative)
the article (Score:3, Informative)
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
Re:I don't care what they say.. (Score:2)
Science is full of ethical questions, bio-sciences especially. What we can do we will do ( as a race ), that's a proven fact. It's better to do what we will do in the open, in front of many eyes, instead of being done in a third world country for some wacked out group intent on bringing their own version of reality to pass.
Re:I don't care what they say.. (Score:2)
Example: biobricks are really advancing, and you can already get custom genes made for a price that anyone can afford. Lets say that biobricks advance to the point where it's relatively trivial to make a gene that produces proteins that create Sarin, for example (or perhaps a different nerve agent with a longer life). You insert the gene into a common strain of phytoplankton found all over the gl
Re:I don't care what they say.. (Score:2)
Just lable the experiments as labratories making weapons of mass destruction. LOL. Bomb. Invade. Elect pro-western government. Move on to next country.
But seriously. With genetic eng
Re:I don't care what they say.. (Score:5, Insightful)
Let's just not forget that there is not such thing as evil knowledge. The way we use it makes good or evil.
Parent
Re:I don't care what they say.. (Score:2)
GE is the technological revolution to shame them all, and will have massive impact on our society.
That said, I'm all for it, and will be first in line for gills.
Re:I don't care what they say.. (Score:3)
Re:I don't care what they say.. (Score:2, Insightful)
"It is the business of the future to be dangerous; (Score:5, Interesting)
-- Alfred North Whitehead, 1927
Parent
I only agree partially... (Score:5, Insightful)
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!
Parent
Re:I only agree partially... (Score:2)
I think there's a slight difference between selective breeding (which determine which of the genes already present in the species get expressed) and introducing new genes which were never before found in that species.
I see nothing wron
Re:I only agree partially... (Score:2)
So, thanks for the criticism :-)
That never stopped anybody... (Score:4, Interesting)
Parent
Re:That never stopped anybody... (Score:2)
Yeah, that made me feel good about the USA. President Truman was told, we are doing the math, and we are 35% done, and so far we have not found a spike in the graph which indicates the nuclear explosio
Re:That never stopped anybody... (Score:2)
Re:That never stopped anybody... (Score:2)
Re:I don't care what they say.. (Score:2, Insightful)
Re:I don't care what they say.. (Score:4, Insightful)
As time goes on, we defeat simple diseases such as the bubonic plague, then upgrade to tougher ones like smallpox. We're now at the point where the only communicable diseases that are seriously fatal are biologically engineered bacteria, and viruses. On top of that, we've still got Cancer to worry about, which is kicking our asses.
While it may be cheaper to produce drugs for everyone alive and distribute them to everyone, no company in their right minds would do this. But if we could figure out genetically how to teach our immune systems to deal with cancer, and certain foreign invaders, we could save millions simply by changing our children's genes.
I think the biggest paranoia attributed to genetic engineering is the fear of change; just because we know how something works now, and we assume that it'll continue working the same way into the future, we give up the notion that we can change things for the better or for the worse. Yes, we are foulable creatures, but at the same time, we now know how to clean up our mistakes. It's far past time we take our fates into our own hands. Why use medicines that can screw up other things in our bodies when we can simply prevent the problem from occuring naturally?
Parent
Re:I don't care what they say.. (Score:2)
Re:Is X-SCID a DiVx format? (Score:4, Funny)
>
> Just wondering.
Funny you should ask. I just got this video from Paul Simon.
It's a turn-around jump shot
It's everybody jump start
It's every moderator throws a hero up the crackpipe
Singin' filk is magical and magical is pain, think of the boy in the plastic bubble
I'm a Slashbot with a baboon brain
(And I believe)
These are the days of lasers on a shark's head,
Lasers on a shark's head somewhere,
Staccato signals of constant information,
A loose affilliation of megabytes
And gigabytes and baby...
These are the days of miracle and wonder,
This is a long-distance boast,
The way the duplicate posts appear in slo-mo,
The way we go for first post.
The way we look to a Netcraft BSD troll,
That's dying like a server at NewSci,
These are the days of miracle and wonder
And don't cry baby, don't cry...
Parent
Re:having RTFA, (Score:2, Informative)
Also, the large percentage of blood consisting of the red blood cells and platelets don't actually have any DNA in them to be mutated - these cells don't have nuclei.
Finally, in bone marrow transplants, one method of collecting the marrow cells to transplant is to hook the donor up to a machine through which their b