On Fri, 7 Jan 2000, Eugene Leitl wrote:
>
> .. and of course greatly preferable to using bacteria (there are bacteria
> which can exist within animal cells, but not too many, and they will be
> definitely hard to control).
All of the Mycobacteria and probably some of the ultra-micro bacteria
strains are probably adaptable. The "control" problem is easy to solve
since you can engineer in suicide triggers. I think the advantage to
bacteria is that you can really "engineer" them to be high production
factories.
>
> 1) Immunoreaction takes time to gear to full response
You are going to get some inflamation as soon as the proteins get
displayed in the MHC complexes, that should only be a matter of
hours after you turn on the protein production. I agree a large
reaction would take immune system amplification and that would
take days to weeks.
Now how long you have to worry about this depends on how fast you
can produce sufficient protein concentration to allow the next stage
of the cool down. You can't cool down too much while you are still
producing the protein because you reduce protein production.
> 2) Immunoreaction can be supressed (and, with a typical patient, is
> not in the best shape anyway)
This seems to be a good solution for cryonics but a bad solution for
long-term gene "enhancements".
>
> We're talking about the end of your biological life span, something
> taking few days or weeks at best. The problem is having a quantitative
> tranfection vector targeting neural tissue without destroying it.
The real trick is "quantitative", one of the reasons the cryoprotectant
fluids are so viscous is because the concentrations are so high.
What you would like is a low concentration fluid that "sticks" once
inside. Then you could pump it in at low concentrations but it would
get selectively concentrated to higher and higher levels in the cells.
> Doing it before (say, at birth) is very risky since gene
> insertions are never quantitative and not as targeted as we would wish
> (I don't think a walking bag of carcinomas is a tolerable side effect).
Adeno-Associated Virus insertions are fairly specific, as would be
insertions managed by the VDJ-recombinase (normally used in tuning
the immune system). What we need and currently lack (to my knowledge)
is a general understanding of how one gets site (sequence) specificity
for things like the AAV/VDJ insertion enzymes or even general gene
promoters (Zn fingers, leucine zippers, etc.). Once we understand that
information we should be able to engineer factors that target insertions
to highly specific locations. The *real* problem however is that if
you need anything more than a few 10's of kilo-bases for your
cryoprotectant "system", the current vectors are simply too small
and will likely remain that way for some time. Threading 100K
of DNA through a nuclear pore into the nucleus is not going to be an
easy problem to solve. Given this fact, a bacterial system begins to
look much more attractive.
This is the same problem we face in "reversing" aging in adults
and is something I've devoted a lot of thought to. Biobots with
supplemental genomes are I think the way to go until nanobots become
feasible. Cryoprotectant manufacturing vehicles would be an interesting
application because you don't have the normal approval headaches
since the person is technically "dead". However, this isn't exactly
a "booming" market.
Robert
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