New, Reversible CRISPR Method Can Control Gene Expression While Leaving DNA Sequence Unchanged (phys.org) 20
fahrbot-bot shares a report from Phys.Org: Over the past decade, the CRISPR-Cas9 gene editing system has revolutionized genetic engineering, allowing scientists to make targeted changes to organisms' DNA. While the system could potentially be useful in treating a variety of diseases, CRISPR-Cas9 editing involves cutting DNA strands, leading to permanent changes to the cell's genetic material. Now, in a paper published online in Cell on April 9, researchers describe a new gene editing technology called CRISPRoff that allows researchers to control gene expression with high specificity while leaving the sequence of the DNA unchanged.
The classic CRISPR-Cas9 system uses a DNA-cutting protein called Cas9 found in bacterial immune systems. The system can be targeted to specific genes in human cells using a single guide RNA, where the Cas9 proteins create tiny breaks in the DNA strand. Then the cell's existing repair machinery patches up the holes. Because these methods alter the underlying DNA sequence, they are permanent.
That's where the researchers saw an opportunity for a different kind of gene editor -- one that didn't alter the DNA sequences themselves, but changed the way they were read in the cell. This sort of modification is what scientists call 'epigenetic' -- genes may be silenced or activated based on chemical changes to the DNA strand. Epigenetic gene silencing often works through methylation -- the addition of chemical tags to to certain places in the DNA strand -- which causes the DNA to become inaccessible to RNA polymerase, the enzyme which reads the genetic information in the DNA sequence into messenger RNA transcripts, which can ultimately be the blueprints for proteins. With this new CRISPRoff technology, one can [express a protein briefly] to write a program that's remembered and carried out indefinitely by the cell.
The classic CRISPR-Cas9 system uses a DNA-cutting protein called Cas9 found in bacterial immune systems. The system can be targeted to specific genes in human cells using a single guide RNA, where the Cas9 proteins create tiny breaks in the DNA strand. Then the cell's existing repair machinery patches up the holes. Because these methods alter the underlying DNA sequence, they are permanent.
That's where the researchers saw an opportunity for a different kind of gene editor -- one that didn't alter the DNA sequences themselves, but changed the way they were read in the cell. This sort of modification is what scientists call 'epigenetic' -- genes may be silenced or activated based on chemical changes to the DNA strand. Epigenetic gene silencing often works through methylation -- the addition of chemical tags to to certain places in the DNA strand -- which causes the DNA to become inaccessible to RNA polymerase, the enzyme which reads the genetic information in the DNA sequence into messenger RNA transcripts, which can ultimately be the blueprints for proteins. With this new CRISPRoff technology, one can [express a protein briefly] to write a program that's remembered and carried out indefinitely by the cell.
Sounds appropriate to /. (Score:2, Interesting)
From TFA: "...Problems with a cell's epigenetics are responsible for many human diseases such as Fragile X syndrome...
Useful (Score:1)
This could be helpful in acheiving In-vitro gametogenesis .. that is taking a skin cell from any person and turning it into a viable egg or sperm cell. That would couples who canâ(TM)t have kids due to medical conditions to be able to have kids. Nature or God is making it really easy for us. Almost like it knows this is the next step in human evolution. Nature made it much harder to do things like make ultra high energy density batteries or travel faster than light. Nature wants us to do this. That
Re: Useful (Score:2)
The star man, the next step in evolution. He records and knows the expressions of genes well adapted to any environment, and can bring them back as needed. New ice age? extinct neanderthal genes appear to make -10 feel comfy. Hot age? lithe Ethiopian forms for all to dissipate heat. All planets and their lifeforms including himself are his (or her) expressions.
You can game it all out in computer simulations, the greatest achievement of genetic evolution is that system which allows for transcendence of the
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Re:Drunken question, how does it undergo methylati (Score:5, Informative)
I see DNA as being a _tightly_ folded chain, very very very long and tightly folded, perhaps into a ball
Mostly correct. Well sort of ... I'd say close enough.
(Where does DNA actually lie within a cell? is it a glob over in the corner?)
It's in the middle in a "cell within the cell" called a nucleus. The DNA can usually be found organized as chromosomes.
Based on that, where/how can the fatty (acids?) bind to the DNA chain? (Methylation.) Doesn't the DNA "cluster" lack room?
Not all of the DNA is inaccessible. A lot of the DNA is wrapped around histones but a lot of it isn't. In fact, it gets unwound and rewound many places, it's quite dynamic.
I'm under the impression that the folding of proteins is very specific, and if they're folded wrong, an incorrect behavior is observed. Does DNA itself not undergo folding? Different folding? unfolded before use? (If unfolded before use, how does proper or sufficient folding take place with methylation, or such to allow methylation to occur?)
Yes, DNA does fold but it can't form all the crazy structures like proteins or even RNA. The process is a little complicated to explain fully without some basics (that's why college is years long) but I'll say that DNA's structure is dependent on a lot of things such as its sequence, what proteins are bound to it, etc. It can often be in a configuration when it can get methylated.
Buy and read a book called "The Cell" latest edition (maybe 6?) by Bruce Alberts. Uh or watch youtube videos and read Wikipedia I guess.
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Haha, Biology is the only college-level (or high school-level) science course that I haven't had. I always wanted to, but scheduling conflicts.
"Histones" came out to be the core of my interest here. Thank you for the summary! I learned a good deal, and wikipedia is helping me through some of it. :-)
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Without any understanding of it myself, look at it this way. When a cell reproduces, it needs to copy the DNA. There are definitely things that happen in the cell that will open up DNA to do work and CRISPR gene editing piggbacks onto these things
Another Nobel in the Making (Score:2)
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Honestly, CRISPR/Cas9 itself is fascinating even from the point of how it works as a bacterial immune system. First off I never would have guessed that bacteria had adaptive internal immune systems. But then it's mechanism is just so bloody clever. An attacking bacteriophage works its DNA into a bacterial genome, but is unlucky enough to insert it into a special-function stretch of DNA containing distinct palendromic repeats. Instead of getting expressed to mRNA to make proteins, these are expressed as t
Software analogy (Score:2)
Epigenetics = Runtime Configuration Settings
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Gene expression can change during your life [sciencedaily.com].
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Yeah, producing a new binary. In order to get the new code running, you have to launch a new process. You don't have to terminate the old process, but it doesn't change either.
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Impact for allergies (Score:2)
heyy (Score:1)
celiac genetic switch Off (Score:2)
I’ll volunteer to rid the curse of intolerance to wheat, barley and rye. Surely, it was switched on, they have a good chance to switch it off. Celiac affects 3% worldwide DQ2+DQ8 except asian genetics differ where it is extremely rare mostly C4 prevalent.