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RNAI - Sirna Therapeutics - Deel 2

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  2. [verwijderd] 2 oktober 2006 14:50

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    The Nobel Prize in Physiology or Medicine 2006
    English
    Swedish

    Press Release
    2 October 2006

    The Nobel Assembly at Karolinska Institutet has today decided to award

    The Nobel Prize in Physiology or Medicine for 2006

    jointly to

    Andrew Z. Fire and Craig C. Mello

    for their discovery of

    "RNA interference – gene silencing by double-stranded RNA"

    Summary

    This year's Nobel Laureates have discovered a fundamental mechanism for controlling the flow of genetic information. Our genome operates by sending instructions for the manufacture of proteins from DNA in the nucleus of the cell to the protein synthesizing machinery in the cytoplasm. These instructions are conveyed by messenger RNA (mRNA). In 1998, the American scientists Andrew Fire and Craig Mello published their discovery of a mechanism that can degrade mRNA from a specific gene. This mechanism, RNA interference, is activated when RNA molecules occur as double-stranded pairs in the cell. Double-stranded RNA activates biochemical machinery which degrades those mRNA molecules that carry a genetic code identical to that of the double-stranded RNA. When such mRNA molecules disappear, the corresponding gene is silenced and no protein of the encoded type is made.

    RNA interference occurs in plants, animals, and humans. It is of great importance for the regulation of gene expression, participates in defense against viral infections, and keeps jumping genes under control. RNA interference is already being widely used in basic science as a method to study the function of genes and it may lead to novel therapies in the future.
  6. nbvdb 3 oktober 2006 16:26

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    Erg leuk dat er nu de erkenning is van een nobelprijs!!! Zat er aan te komen overigens.

    Anna, goed gevonden al die recente artikelen over RNAi doorbraken!

    De gedachte komt onvermijdelijk bij me op hoe het staat met de onderzoeken van SIRNA met Eli Lilly. Daar hoor ik in elk geval weinig van en het valt me op dat er op de SIRNA website niet eens een aparte oncology page is. Terwijl dat toch algemeen gezien wordt als een van de meest veelbelovende terreinen voor siRNA onderzoek, wat ook wel blijkt uit de recente doorbraken.

    Ik kan niet wachten tot er ook op dat gebied duidelijk vooruitgang gemeld wordt (al zijn die milestone betalingen niet voor niets gegeven)
  7. [verwijderd] 3 oktober 2006 16:28

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    quote:

    nbvdb schreef:

    De gedachte komt onvermijdelijk bij me op hoe het staat met de onderzoeken van SIRNA met Eli Lilly. Daar hoor ik in elk geval weinig van en het valt me op dat er op de SIRNA website niet eens een aparte oncology page is. Terwijl dat toch algemeen gezien wordt als een van de meest veelbelovende terreinen voor siRNA onderzoek, wat ook wel blijkt uit de recente doorbraken.

    Ik kan niet wachten tot er ook op dat gebied duidelijk vooruitgang gemeld wordt (al zijn die milestone betalingen niet voor niets gegeven)
    Dat onderzoek is afgerond, sirna is vrij om een andere partner te zoeken. Volgens mij gaat sirna het product eerst zelf gedeeltelijk ontwikkelen voor verschillende indicaties. Dan kunnen ze er veel meer voor vragen.
  8. [verwijderd] 3 oktober 2006 20:13

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    Voor de liefhebbers, veel mbt RNAi in Nature:
    Published online: 2 October 2006 | doi:10.1038/news061002-2
    RNAi scoops medical Nobel
    Gene silencers get something to shout about.
    Michael Hopkin

    Two US geneticists who discovered one of the fundamental mechanisms by which gene expression is controlled have received a Nobel prize for their achievement. Andrew Fire and Craig Mello, who revealed the process of RNA interference (RNAi) in 1998, will share the US$1.4-million award.

    RNAi, which occurs naturally in plants and animals, allows a gene to be specifically 'silenced'. This helps to regulate gene expression, and protects against viral infection and 'jumping genes' that can replicate and spread through the genome.

    The process can also be induced experimentally by injecting tailor-made genetic sequences into cells, giving scientists a method for deliberately silencing a target gene. The method is now widely used as a basic genetic tool and is a promising candidate for future therapies.

    "They have opened up a whole new area of biology, which was unsuspected before," says Nick Hastie, director of the Medical Research Council Human Genetics Unit in Edinburgh, UK. "It is also one of the quickest recognitions of a discovery; to find this in 1998 and get a Nobel Prize in 2006 is remarkable."

    Worm turns
    Fire, then working at the Carnegie Institution of Washington in Baltimore, Maryland, and Mello, who was at the University of Massachusetts Cancer Center in Worcester, made the discovery when studying the worm Caenorhabditis elegans, a much used workhorse for research geneticists.

    They were investigating the process by which the information encoded in genes, made of DNA, forms a template for the manufacture of proteins — the 'central dogma' of molecular biology. The first step of this process is the transcription of the DNA code, housed in the cell nucleus, into a related molecule, messenger RNA (mRNA), which exits the nucleus.
    Fire, Mello and their team wanted to see whether they could influence the production of muscle protein in the worms by tinkering with the mRNA transcribed from the relevant gene. When they injected more of the naturally produced mRNA, it had no effect. Likewise, when they injected a tailor-made 'antisense' sequence to bind to the natural 'sense' sequence, nothing happened to the worms.

    But when they injected double-stranded RNA made up of both sense and antisense sequences bound together, the worms displayed twitching behaviour similar to that of genetic mutants with no muscle gene at all. They had silenced the gene.

    Subsequent investigation showed that injecting specific double-stranded RNA can silence any gene, and that you only need to inject a few molecules to do it. When Fire and Mello published their findings in Nature1 in 1998, a new world was opened to geneticists.

    Inside story

    Fire and Mello also unravelled the mechanism by which the gene interference works, and the reason why simply injecting antisense RNA doesn't silence genes.

    Double-stranded RNA is recognized by a protein called Dicer, which breaks it up into tiny double-stranded fragments. These fragments are then bound by a protein complex, RISC, which strips away one of the strands, leaving a complex bearing a tiny strip of RNA. (Although this process results in single strands, starting with a single strand of RNA does not have the same effect as it activates neither Dicer nor RISC).
    On the defence

    The mechanism serves as a natural defence against viruses, which attempt to co-opt a host's protein-production mechanism by inserting their own genes into the host DNA. The process also protects a cell from rampant expression of host gene fragments that replicate and insinuate themselves all over the genome.

    New opportunities for using the technique are still emerging. Besides fighting viral infection, the method could be adapted to combat cancer, endocrine disorders and cardiovascular disease.

    In animal trials, RNAi was recently successful in silencing a gene that causes high cholesterol levels. But other work has sounded an alarm about the potential dangers of RNAi — one recent trial, for example, showed that it could prove fatal to mice (see 'RNA treatment kills mice') . Researchers are approaching clinical trials with caution.
    Some have referred to the discovery as ushering in an RNA revolution, because it overrides the previous assumption that DNA is in control. In a 2004 review, Mello replied that "it is perhaps more apt to call it an RNA 'revelation'. RNA is not taking over the cell — it has been in control all along. We just didn't realize it until now."

    www.nature.com/news/2006/061002/full/...

    The original Fire and Mello paper from 1998.
    www.nature.com/nature/journal/v391/n6...

    Celebrating some groundbreaking work from 2004, here find a collection of hot research papers and an animation of RNA interference.
    www.nature.com/focus/rnai/animations/...
    www.nature.com/focus/rnai/animations/...
  16. [verwijderd] 6 oktober 2006 16:37

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    Net er wel even onder. Maar dat gebeurde voor sluiting ook al, blijkbaar geen weerstand en geen steun.

    Alles wordt wel mooi opgevangen. Vraag me af hoeveel het omhoog gaat op het volgende nieuws.
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