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Severe combined immune deficiency

  1. Dec 2, 2003 #1

    Monique

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    I thought it was interesting to note that out of 15 SCID (severe combined immune deficiency) patients cured by retroviral gene therapy, 2 developed leukemia.

    This as a direct integration of the virus into a pro-oncogene, the interesting thing is that both patients had an insert in the same gene! (LMO-2)

    This poses questions on the safety of gene therapy. Ofcourse, not all virusses integrate themselves into the genome (like adeno, or adeno-associated virusses) but those other ones bring severe immunological risks with them..


    I wonder, wouldn't it be possible to target a virus to a specific 'junk region' of the genome? I am not sure how virusses integrate themselves, they probably depend on regions with less dense histone packing..
     
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  3. Dec 2, 2003 #2

    selfAdjoint

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    Derek Lowe's article

    Derek Lowe had an article about this a month or so ago - you might have to look in his archives for it. Basically what he said is that the attachment links are not randomly distributed in the chromosome, and that the probablility that your vector will attach near a leukemia site cannot be estimated by uniform distribution, which is what the experimentalists did. How the attachment points really are distributed, and why they seem to nestle close to leukemia sites is material for future research.
     
  4. Dec 2, 2003 #3

    Monique

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    I looked in the archives, but didn't find anything.

    So how did these researchers know it is not uniformly distributed and is not random? I agree that lightning striking the same spot twice is suspicious, but since these are specific blood cells which will require a specific growth hormone, it might not be that striking that cells with this particular mutation have a growth advantage.

    How did they find this gene in particular to be faulty anyway? Maybe there are a dozen more of the same genes defective in the same patients?
     
  5. Dec 2, 2003 #4

    selfAdjoint

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    I'll see if I can find the paper/
     
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