The New Discovery

[frogus]

I'm sure many people besides me read this story in the paper yesterday...so what do you make of it? In five years will the world be free of AIDS and cancer? What do you think the results of this discovery will be? Are you skeptical? Will it lead to real changes to life and the world, or is it just another news story?

[Nightmare]

I think it would be great, although one question pops to mind: What will it cost? They could charge literally thousands and thousands of dollars to people, and people would pay that to save their lives. And what about people that don't have that money?

Although, I'm a little skeptical about a cure anyway...

[C Elegans]

Whenever new, unexpected groundbreaking discoveries are made, people are quick to dream of all the possibiliies. The finding that RNA can silence genes, is a major finding in modern molecular genetics and it has already proved useful. Whether it will help us find a cure for HIV and other retrovirus infection, or a cure for cancer, is still speculation although the usefulness for curing HIV certainly is much closer than cancer.

It is not "just another news story", but I am surprised the newspaper make something of this now and not a month ago when the HIV cell experiements were reported in the scientific press.

Anyway, I am sure the RNA silencing of genes will be a very useful tool in our attempts to understand more about genetics and postgenetics generally, and perhaps also in our attempts to find a cure for various diseases. Sadly however, Gaxx is right in his observation - whatever the medical benefits will be, they will be expensive and only available for a small group of people. Just look at modern medicine - 40 years ago the life saving by pass heart surgeries where new and groundbreaking, today, we take it for granted that everybody can have them. That is, everybody in the rich world. For 9/10 of the population, a by pass surgery is still only a dream. It is the same with all medical advances. The poorest people on earth can't even afford antibiotics.

[Dottie]

Originally posted by C Elegans
and perhaps also in our attempts to find a cure for various diseases.

As a person in the rich world... What about change of hair color?

[C Elegans]

Originally posted by Dottie
As a person in the rich world... What about change of hair color?

You don't need RNA silencing of genes to change you hair color, it can be done with the the old standard genetic engineering already in use. However, these methods are not for commercial use (yet), so you will have to make do with a bottle for some time to come.

[Dottie]

Oh... I had no idea... No chance to submitt oneself as test subject either?

[Tybaltus]

Originally posted by Dottie
Oh... I had no idea... No chance to submitt oneself as test subject either?

I dont know if that would be such a good idea. I mean, they could make a critical mistake or something, and your hair could be permanently changed into something resembling plaid, or something else bad. Those consequences loom when they do experiments.

[Dottie]

Originally posted by Tybaltus
and your hair could be permanently changed into something resembling plaid

Im more then willing to take the risk...

[C Elegans]

@Tyb: LMAO

Originally posted by Dottie
Oh... I had no idea... No chance to submitt oneself as test subject either?

There are no human experiments in this area yet...besides, so far, genetic engineering can't be done successfully at adults, you must build in the new genes in an embroy. So it's too late for you anyway.

Hrm, maybe you should quit spamming Frogus thread and comment on his opening post instead?

[Dottie]

Originally posted by C Elegans

There are no human experiments in this area yet...besides, so far, genetic engineering can't be done successfully at adults, you must build in the new genes in an embroy. So it's too late for you anyway.

But I thought that was the point of RNA silencing? If not, then how could it be used to cure cancer or HIV?

Yes... im sorry for my bad self-discipline frogus..

[C Elegans]

Originally posted by Dottie
But I thought that was the point of RNA silencing? If not, then how could it be used to cure cancer or HIV?

It is, I said so far. What I meant was that the hietherto used methods of genetic engineering, ie replacing a gene or a gene sequence with another, (like with knock-out or knock-in animals, animals where one specific genes has been removed or added) has not been successful on adult specimen. However, this RNA interference (RNAi) is a totally different type of method, and it hasn't been done on mammals at all, only at plants, worms, flies and cultured cells. The HIV stuff was done on mammalian cultured cells, which of course is promising. Here is an extract from the real article, the one that was mentioned in Frgous link. The last paragraph also explains a hypothesis RNA can have this effect on genes.

25 July
Nature 418, 435 - 438 (2002)
Nature AOP, published online 26 June 2002

Modulation of HIV-1 replication by RNA interference

JEAN-MARC JACQUE, KARINE TRIQUES & MARIO STEVENSON

RNA interference (RNAi) is the process by which double-stranded RNA (dsRNA) directs sequence-specific degradation of messenger RNA in animal and plant cells1, 2. In mammalian cells, RNAi can be triggered by 21-nucleotide duplexes of small interfering RNA (siRNA)3 . Here we describe inhibition of early and late steps of HIV-1 replication in human cell lines and primary lymphocytes by siRNAs targeted to various regions of the HIV-1 genome. We demonstrate that synthetic siRNA duplexes or plasmid-derived siRNAs inhibit HIV-1 infection by specifically degrading genomic HIV-1 RNA, thereby preventing formation of viral complementary-DNA intermediates. These results demonstrate the utility of RNAi for modulating the HIV replication cycle and provide evidence that genomic HIV-1 RNA, as it exists within a nucleoprotein reverse-transcription complex, is amenable to siRNA-mediated degradation.

RNAi is a ubiquitous mechanism of gene regulation in plants and animals4 in which target mRNAs are degraded in a sequence-specific manner5 . RNAi is initiated by the dsRNA-specific endonuclease Dicer, which promotes processive cleavage of long dsRNA into double-stranded fragments between 21 and 25 nucleotides long, termed siRNAs5-8. Small interfering RNAs are incorporated into a protein complex that recognizes and cleaves target mRNAs9 . Introduction of dsRNA into mammalian cells does not result in efficient Dicer-mediated generation of siRNA and therefore does not induce RNAi10, 11 . The requirement for Dicer in maturation of siRNAs can be bypassed by introducing synthetic 21-nucleotide siRNA duplexes, which inhibits expression of transfected and endogenous genes in a variety of mammalian cells3 . HIV-1 uses RNA intermediates in its replication. Therefore, we examined whether siRNA duplexes specific for HIV-1 were capable of effecting the degradation of viral RNAs necessary for completion of early and late events in the viral replication cycle.

We directed 21-nucleotide siRNA duplexes against several regions of the HIV-1 genome, including the viral long terminal repeat (LTR) and the accessory genes vif and nef (Fig. 1a). Small interfering RNA duplexes were co-transfected with an HIV-1 molecular clone (HIVNL-GFP; ref. 12) into CD4-positive HeLa (Magi) cells13 . Transfection of cells with an infectious molecular HIV-1 clone recapitulates late events in the viral life cycle, including production of viral RNAs, translation of viral proteins and release of virions. Compared with cells not transfected with siRNA duplexes, virus production, measured 24 h after transfection, was reduced 30-fold to 50-fold by homologous siRNAs (Fig. 1b). HIV production was inhibited to a lesser extent by single mismatch siRNAs (MTAR, M441), whereas a vif siRNA with four mismatches (M98) did not inhibit HIV production (Fig. 1b ). Activation of the dsRNA-activated protein kinase PKR leads to an inhibition of protein translation in a sequence-non-specific manner relative to the inducing dsRNA. Activation with PKR was not involved in the inhibition of the negative-strand RNA virus RSV (respiratory syncytial virus) by siRNAs14 . Similarly, there was no significant induction of activated PKR (phosphorylated on Thr 446) over levels in non-transfected cells by any of the siRNAs (Fig. 1c).
<snip>
We next examined whether siRNAs could inhibit HIV gene expression (GFP fluorescence) in primary peripheral blood lymphocytes (PBLs), which are natural targets for HIV-1 infection. The frequency of GFP-expressing cells was markedly reduced in cells transfected with homologous siRNAs (T98, G388, nef) relative to cells transfected with mismatched siRNAs or non-transfected cells (Fig. 1e). The level of HIVNL-GFP RNA, as determined by polymerase chain reaction with reverse transcription (RT–PCR), was also markedly reduced in cells transfected with homologous siRNAs (results not shown). Therefore, the components of siRNA-activated RNAi are fully functional in cells naturally targeted by HIV-1 infection.
<snip>
The involvement of RNAi in transposon silencing21, 22 suggests that RNAi is an ancient antiviral system that may have evolved as a defence mechanism to protect the host from invasion by mobile genetic elements including transposons and viruses. Several studies have indicated that it is difficult to induce RNAi in mammalian cells using long dsRNAs. Although long dsRNAs can modestly inhibit gene expression in mammalian cells, the effects are not sequence specific3, 23 and are more consistent with inhibition by the interferon response. Intriguingly, it is now becoming apparent that underlying the non-specific dsRNA-activated interferon response in mammalian cells, there may indeed be a sequence-specific RNAi effect that can be activated by long dsRNA24-26. Silencing by long dsRNAs has now been observed in various cultured mammalian cells24, 25 . The mechanism of silencing is consistent with RNAi because there is evidence that the long dsRNAs are processed to siRNAs and target RNAs are specifically degraded. Our results indicate that 21-nucleotide siRNAs promote HIV RNA degradation in primary lymphocytes, suggesting that the major target cell for HIV replication possesses functional components of the siRNA-induced silencing complex that mediates specific cleavage of target RNA2 . Future studies should determine whether sequence-specific RNAi that is independent of the interferon response can be activated against HIV by long dsRNAs.

[Mr Sleep]

Correct me if i am wrong (please do, i might have been mis infomed) but aren't the close to finding a cure for AIDS in the moden world and can not apply the same science to African nations and exotic places due to the difference in genetic make up...this is complete here say, so like i say, correct me

[fable]

Parenthetically, I wonder if this gene silencing technique is also being used in a revolutionary anti-asthma medication that is currently being tested. (Preliminary results look good, but it's not expected to make it to the market for at least another year, possibly two.) Asthma is in some respects a mirror image of HIV, because the immune system is overactive. A threat is perceived where none exists, and the means used to combat the threat is wildly out of control, and damaging to the organism--potentially lethal. (About 100 people still die from asthma each year; tens of milions die from respiratory complications related to asthma, as well.)

The new medication, according to my physician, attacks asthma in a stage much earlier than previous drugs have permitted, preventing the immune system from even sensing the inherent "danger" of innocuous items. If this is gene-specific, then presumably silencing a particular gene strand could allow the immune system as a whole to operate normally. This would be a tremendous boon to COLDs (people suffering from chronic obstructive lung disease).

[wiwimu]

About 100 people still die from asthma each year; tens of milions die from respiratory complications related to asthma, as well.

omg that's terrible....and asthma seem so harmless (at times)...

RNA interference
i wonder if there are any side effects ...sometimes you will never know until 10, 20 years later when it begins to show... modern molecular genetics ...
hmmm very scary the way humans are trying to control their lives...but useful if humans want to be immune to all disease,virus sickness...(not inclusive of the sickness of the mind)
I wonder if in the future there will be super humans that live forever.

[Tybaltus]

Originally posted by wiwimu

omg that's terrible....and asthma seem so harmless (at times)...

RNA interference
i wonder if there are any side effects ...sometimes you will never know until 10, 20 years later when it begins to show... modern molecular genetics ...
hmmm very scary the way humans are trying to control their lives...but useful if humans want to be immune to all disease,virus sickness...(not inclusive of the sickness of the mind)
I wonder if in the future there will be super humans that live forever.

The question is: Would it be a miracle or a curse that a person could live forever? Certainly life is good to live and there are countless things to do and see, but living forever, you have to go through bad things too. I think death is as much a part of life as life, itself is. But Im not exactly sure how to think of it. I know I wouldnt want to live forever, I would like to live a long time, but not forever.

To be immune to such diseases and things that cause premature death I think is what everyone should strive for and it would certainly be a great discovery to end such things.

[wiwimu]

i don't want to live forever and i don't like the idea of humans controlling their own motality rate (by genetic modification). It seems very off balance...but then again i don't think it will ever happen. (Seems like Gaxx_Firkraag has a point)

it's always good for a loved one to be saved by science but it still seems so.... sigh..( i don't know how to put it).

[Bloodstalker]

All I want is a regenerating liver.

And living forever would be something I would not want at all. Besides, if we lived forever, where would we live? There isn't enough room. There would come a point where no one would be allowed to reproduce. Or they would started mandatory execution at a certain age or something to stem overpopulation

[fable]

Originally posted by wiwimu

omg that's terrible....and asthma seem so harmless (at times)...

Asthma's never been harmless, but that's the image that has been promulgated for years: a sort of "fake disease" used by hypochondriacs to justify doing nothing. Now, asthma may have been used for this purpose at some point, by somebody, but as much could be said for other diseases. It's easy to fake a whole range of illnesses. But I strongly doubt that a child of one, let's say, is capable of faking anaphylaxis (that's an acute asthma attack, in which it's next to impossible to force carbon dioxide out of the lungs). I know I've never faked it, and I've had asthma since shortly after birth. That didn't prevent various teachers of mine from expressing the opinion in front of the classroom that my drugs were fakes and that asthma itself was a joke, but you get used to people being acting like idiots, especially in the underpaid teaching profession.

I won't go into a great deal of detail, but asthma is a very dangerous disease that has had me unconscious and near death on a few occasions. Even now, under a regular medical regimen with some of the latest meds, it's still a hassle. I have to make sure I know what's in the food I eat when we go out, and have to be careful not to be scratched by a plant. If I'm in a shop filled with moldy old antiques, I need to drug-up first. You learn to live with it, to accept it, but you'd never call it harmless.

In any case, I'm sure you can understand why I'm excited over the possibilities of this new med-in-development. Current meds treat various symptoms of asthma, either preventatively or during an episode. The idea of getting to the root cause of asthma has always been problematic, since it's been finally realized that at least some aspects of the disease occur at the genetic level. If whatever causes the immune system to go haywire can be stopped, simply stopped, asthmatics like myself will actually face the prospect for the first time of living normal lives.

As you might guess, I'm eagerly awaiting the commercial product.

[wiwimu]

that didn't prevent various teachers of mine from expressing the opinion in front of the classroom that my drugs were fakes and that asthma itself was a joke, but you get used to people being acting like idiots, especially in the underpaid teaching profession.

That's really sorry to hear(especially since they are teachers) but i am glad i have learnt something about how serious asthma can be
(so i won't be one of the idiots) hihi


My brother used to have asthma but it was not very serious my mother fed him some chinese concoction(chinese medicine) that was made from crocodile meat and he recovered after about half a year...(this is true) but i'm not sure if it is medically proven.

[Maharlika]

I understand fully how insensitive...

Originally posted by fable

That didn't prevent various teachers of mine from expressing the opinion in front of the classroom that my drugs were fakes and that asthma itself was a joke, but you get used to people being acting like idiots, especially in the underpaid teaching profession.

...and idiotic these people seem to be, and maybe just maybe it's common among American teachers...

...but where I came from it's these underpaid teachers who tend to be more of heart than insensitive idiots...

...anyways...

...I do hope that new discoveries in genetic engineering can at least help in curing congenital ailments rather than having to live longer/forever.