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Crucell« Terug naar discussie overzicht

$$$ CRUCELL H2 2007 $$$

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  1. [verwijderd] 26 oktober 2007 17:40
    Crucell
    Laatste Volume Tijd
    Laatste 13,58 1.000 17:35:05
    Verschil 0,02 0,1475 %
    Bied 13,51 6.491 17:37:57
    Laat 13,58 5.793 17:37:57
    Hoogste 13,64 09:05:24
    Laagste 13,44 10:39:15
    Cum. volume --- 154.828
    Indicatieve opening ---
    Open 13,60 09:00:10
    Vorig slot 13,56 25-10-2007
    Gemiddelde dagomzet --- 408.052

    Bid Ask
    Orders Volume Bid Ask Volume Orders
    2 6.491 13,51 13,58 5.793 2
    3 3.040 13,50 13,59 1.200 1
    1 3.597 13,49 13,60 4.730 3
    2 11.129 13,48 13,62 5.790 1
    1 2.640 13,46 13,63 11.054 1

    Dree
  2. [verwijderd] 27 oktober 2007 00:29

    The genesis of a unique production platform

    A small company initially focussing on the development of gene therapy products grew out to be a top biotech company with an unique asset: the PER.C6 cell line, a universal production platform for vaccine and protein manufacturing.
    "It all started many years ago with scientific curiosity in how adenoviruses are able to cause cancer. The development was a natural process. When new molecular techniques successively became available forward steps were made," tells Lex van der Eb, one of the fathers of the PER.C6 technology.
    by Astrid van de Graaf

    Professor emeritus dr. Lex van der Eb is, since his retirement eight years ago, Senior Advisor at Crucell in Leiden.
    lt is no coincidence that Dinko Valerio, the founding father and at that time CEO of Crucell, asked him to join the company.
    Van der Eb's research formed the fundamental basis of what is
    now known as the mammalian celline PER.C6. Since his PhD Van der
    Eb has been researching the adenovirus, its ability to induce cancer in
    certain animals and to transform both human and animal cells in culture.

    Adenoviruses are able to reproduce in the nucleus of
    human cells using the host's replication machinery. For that purpose they
    turn the cell into a rapidly dividing cell resembling a cancer cell.
    lt was the end of the sixties when Van der Eb started his work on adenovirus transformation. But much genetic research
    on cancer in those days was unsuccessful. nln retrospect this was not
    surprising. The reason was that the molecular biological tools were simply lacking.

    Calcium phosphate

    However, in the beginning of the seventies, when Van der Eb was asked to start a research group on tumor viruses at the University of Leiden, important developments took place which would lead to big steps forward: the discovery of restriction enzymes and recombinant DNA technology, and the invention of a new technique which
    made it possible to assay infectivity of DNA in mammalian cells. A Canadian post-doc, Frank Graham discovered the latter in Van der Eb's laboratory. It was after almost two unsuccessful years of hard work, just before we decided to stop the project, when Frank found a number of colonies of fast growing cells in the petridishes with rat cell cultures, indicating that the viral DNA had performed its carcinogenic effect.
    The method he used in this last experiment would become
    known as the `calcium phosphate DNA transfection' technique.
    This calcium phosphate method is today,
    after more than thirty years, still one of the best and certainly cheapest
    methods to introduce DNA into mammalian cells.
    With this breakthrough technology Van der Eb was able to transfect rat
    cells with free viral DNA fragments, and turn them into cancer cells with -
    out using intact viruses. This also made it possible to isolate the trans-
    forming viral genes and study their function. But the step to transform human cells had still to be made. nWe used `primary' foetal human kidney cells, rather than human tumor cells that others used because these are more easy to cultivate.D However, surprisingly, the human cells turned out to be resistant to transformation by the human adenovirus. Again and again the experiments were repeat- ed until one day a colony of densely growing cells appeared on a petrid - ish, indicating that an adenovirus- transformed human cell had been created. nFrank tried to isolate the cells immediately since it looked like a once in a life time event.D The cells would become known as 293 cells, so named because it was experiment number 293.

    Although the adenovirus we used is a specific human virus, it was very
    difficult to repeat the experiment. lnspired by literature on rat brain and
    retina cells, which could be very efficiently transformed by human adenovirus, we tried human embryonic retina cells. And that was successful.
    They were able to reproducibly transform human retina cells into
    cancer cells with viral DNA. A few years later we heard that an American
    research group used the 293 cell-line to produce adenovirus vectors for
    gene therapy. So one thing led to the other.
    The idea of gene therapy is to insert a functional gene into cells of a
    patient in order to correct the defective gene and thereby cure the disease. Adenoviruses are an attractive tool for the construction of vectors that can carry the curative gene into patient cells. But in order to insert the gene of interest into the viral DNA, one first has to make room by removing one or more of its viral genes.
    As a result, such viral DNAs can no longer multiply and form viruses as they lack viral genes.
    The trick to circumvent this problem was to create space by deleting specifically the transforming genes from the adenovirus DNA since
    such DNA can still multiply in 293 cells: these cells already contain the
    transforming genes. So the 293 cells could be used as host cells for multi - plying adenovirus vectors

    Entrepeneur in heart and soul
    So far the scientific history part. The other side of Crucell's success story
    started with the former PhD student of Van der Eb, Dinko Valerio, who was besides an excellent researcher and professor in gene therapy, an entrepreneur in heart and soul. He started in 1993 a company called lntroGene dedicated to develop th7 perfect vector for gene transfer.
    We sat down together with scientists of university and lntroGene to think through the properties of the perfect adenovirus vector, the gene constructs and the cell line to multiply the vector. Valerio soon came to the conclusion, that if the project was to succeed, a new cell-line had to be made under GLP conditions, hence should be completely documented and characterised, and that his company needed the exclusive r
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