Speculation on error correction [Re: The fountain of youth.]

Allen Smith allens at yang.earlham.edu
Sat May 16 06:50:30 EST 1992

In article <1992May14.205658.18282 at sci.ccny.cuny.edu>, dac at sci.ccny.cuny.edu (Da
   vid A Cooke) writes:
>>> Once gene therapy is an off the shelf process you will be able
>>> to replace any of your alleles with the "optimal" one for your
>>> lifestyle ...
>>How can broken genes be replaced without also messing up the gene
>>expression state of somatic cells?    For example, if my insullin
>>producing gene is broken, I want to replace it and have the
>>new gene turned on in my pancreas but turned off elsewhere.
>       Unless a damaged gene is producing a product that is a problem in and
> of itself (e.g the mutant hemoglobin produced in people carrying the sickle
> cell trait), there is no reason to turn off the old gene.  A functional copy
> of the gene can be inserted under the appropriate promoter and enhancer,
> and it should be expressed normally.  If the defective gene product itself
> is a problem, antisense therapy might be an option, though granted the
> technique will require a lot more development before that can be considered.
>       As far as targeted expression, there are a number of ways to do
> that.  In many cases, the promoters and enhancers on the gene will produce
> tissue-specific expression, so the transfection need not be selective.
> Another approach is the use of engineered viral vectors that are specific
> to cell type.  A number of natural viruses (most notably AIDS) have this sort
> of specificity; with some clever genetic manipulation they could probably
> be used for this sort of therapeutic purpose.  A third option, already being
> used in human experimental trials, exists for certain types of cells, such
> as marrow-derived cells.  The marrow can be removed, transfected with the
> desired DNA, and replaced.  The cells subsequently produced from this marrow
> will carry the desired trait.  A fourth, and perhaps simpler, solution may
> involve using foreign cells.  A paper published in Science earlier this year
> described curing Type I diabetes in rats by implanting foreign insulin-
> producing cells in nonbiological cylinders into the rats abdomen.  The
> cylinders shielded the cells from the host immune responses, but allowedd
> them to exchange nutrients and wastes with the blood, as well as release
> of insulin.  The result was that these rats  produced insulin in a normal
> regulated manner and were cured of diabetes, all without tissue rejection.

        Has much work been done with the idea of taking cells out, doing
gene therapy on them, then implanting them back in- where they aren't
normally? For instance, most if not all the side effects of testosterone
and somatotropin, when used for body-building, are due to their travelling
places other than the muscles and similarly beneficial spots. An idea I've
had was to take cells from other portions of the body, modify them to
produce a short-lived form of testosterone or growth hormone (this would
be the hardest part, admittedly; but I'd think that in researching
artificial forms of testosterone that at least a few short-lived forms
would have been come across, although implementing them in a biological
system might be difficult), then implant them into the muscles and other
        If one is simply trying to target the effects of a drug or hormone,
then it needn't neccessarily be the cells that normally produce it that
get altered. Just alter some cells from the person (avoiding immunological
problems) and implant them in the correct location.

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