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[S.Daily] Non-Lethal Way of Switching Off Essential Genes in Mice Perfected

post #1 of 17
Thread Starter 
Quote:
ScienceDaily (Apr. 14, 2011) — One way of discovering a gene's function is to switch it off and observe how the loss of its activity affects an organism. If a gene is essential for survival, however, then switching it off permanently will kill the organism before the gene's function can be determined. Researchers at Cold Spring Harbor Laboratory (CSHL) have overcome this problem by using RNA interference (RNAi) technology to temporarily turn off any essential gene in adult mice and then turn it back on before the change kills the animals.

Source
This will have HUGE improvements to knockdown techniques.

Reference:
Cold Spring Harbor Laboratory. "Non-lethal way of switching off essential genes in mice perfected." ScienceDaily, 14 Apr. 2011. Web. 16 Apr. 2011.
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post #2 of 17
Oh, your annotating skills!

This is very good.
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post #3 of 17
One step closer to Government instructed gene pools.
    
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post #4 of 17
RNAi has already been used for a while, but only to propogate the knockdown to offspring. This new in-vivo method seems quite interesting...
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post #5 of 17
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Quote:
Originally Posted by kz26 View Post
RNAi has already been used for a while, but only to propogate the knockdown to offspring. This new in-vivo method seems quite interesting...
Absolutely
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post #6 of 17
I haven't read the paper, but it sounds like the main news here is the 'porting' of an old technology to a new model organism and polishing it (previously used in the animal model; Caenorhabditis elegans [nematode worm]).

The way I see it, they transfected a mouse embryo to express a palindromic sequence complementary to this DNA-replication cofactor’s sequence (RPA3). This sequence (when transcribed) would fold into a double stranded RNA hairpin structure, activating the RNAi pathway (RISC/Dicer) destroying the RPA3’s RNA. This sequence will have been flanked by an inducible promoter (tetracycline was mentioned) and fused to a marker; some form of fluorescent protein sequence (maybe had its own copy of the promoter).

In C. elegans, you just had to soak the worm in double-stranded RNA complementary to the gene which you wanted to knockdown, which worked as all the cells took it in (only around 1000 cells to diffuse too). However this doesn't work in the mouse because the RNA wont enter all the cells (to put it simply). This new method would get around that by inducing all the cells to produce the double-stranded RNA with something which can reach all the cells (by diffusing in via the bloodstream), thus causing the temporary knockdown of the target sequence for as long as the inducer is present.

The real world advantages of this would be the easier, quicker and thus cheaper development of therapeutic drugs (quicker: potential targets can be tested to see if disrupting their function actually has an effect before developing the drug [Finding a molecule which binds to and disrupts the function of a target protein is a long and costly process]. Easier: less trial and error due to the previous point.)

Because mice are genetically much closer to humans than nematode worms, they make much better disease models. This method specialises in the study of genes which cause ‘embryoic lethality’ when knocked out in the embryo, and so allows the study of these genes which maybe have mutated and caused the uncontrolled proliferation of cells (as in the case of cancer).
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post #7 of 17
Thread Starter 
Quote:
Originally Posted by DTK View Post
I haven't read the paper, but it sounds like the main news here is the 'porting' of an old technology to a new model organism and polishing it (previously used in the animal model; Caenorhabditis elegans [nematode worm]).

The way I see it, they transfected a mouse embryo to express a palindromic sequence complementary to this DNA-replication cofactor’s sequence (RPA3). This sequence (when transcribed) would fold into a double stranded RNA hairpin structure, activating the RNAi pathway (RISC/Dicer) destroying the RPA3’s RNA. This sequence will have been flanked by an inducible promoter (tetracycline was mentioned) and fused to a marker; some form of fluorescent protein sequence (maybe had its own copy of the promoter).

In C. elegans, you just had to soak the worm in double-stranded RNA complementary to the gene which you wanted to knockdown, which worked as all the cells took it in (only around 1000 cells to diffuse too). However this doesn't work in the mouse because the RNA wont enter all the cells (to put it simply). This new method would get around that by inducing all the cells to produce the double-stranded RNA with something which can reach all the cells (by diffusing in via the bloodstream), thus causing the temporary knockdown of the target sequence for as long as the inducer is present.

The real world advantages of this would be the easier, quicker and thus cheaper development of therapeutic drugs (quicker: potential targets can be tested to see if disrupting their function actually has an effect before developing the drug [Finding a molecule which binds to and disrupts the function of a target protein is a long and costly process]. Easier: less trial and error due to the previous point.)

Because mice are genetically much closer to humans than nematode worms, they make much better disease models. This method specialises in the study of genes which cause ‘embryoic lethality’ when knocked out in the embryo, and so allows the study of these genes which maybe have mutated and caused the uncontrolled proliferation of cells (as in the case of cancer).
Well phrased!
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post #8 of 17
Can't wait to see this being used in pharmaceuticals.
post #9 of 17
I can't wait to see giant MICE MONSTERS!



I jest but...
post #10 of 17
So.. much... SCIENCE!
    
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