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Science Forum Index » Nanotechnology Forum » Nano-rod Gene Delivery
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| sanman |
 Posted: Thu Oct 16, 2003 11:20 pm |
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| Joann Evans |
| Posted: Fri Oct 17, 2003 10:16 am |
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sanman wrote:
Clearly not an issue of 'rather than' but 'sooner than.'
--
You know what to remove, to reply.... |
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| Gordon D. Pusch |
| Posted: Fri Oct 17, 2003 10:43 pm |
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manofsan@yahoo.com (sanman) writes:
As attempts to use retorvirii to transfer gene have shown, it is =NOT=
sufficient to simply "deliver" genes to cells, since genes spliced in
at random locations in random cells are highly unlikely to be properly
regulated, and often result in cancer, or even death of the patient.
For gene therapy to become practical, we must develop _targeted_ gene
delivery mechanisms that will ensure that therapeutic genes are only spliced
into the correct locations in the patient's DNA, complete with any flanking
regulatory regions, and are only expressed in the correct types of somatic
cell.
(Alternatively, a complete gene complex might be delivered as a complete
"mini-chromosome" containing all the genes and control regions required to
fill in for the malfunctioning portions of the patient's own metabolism,
and including some sort of fail-safe mechanism that will cause it to
inactivate itself if it finds itself in the wrong type of cell.) While
this sort of "targeted" therapeutic gene delivery might not require fully
programmable drexlerian nanobots, it almost certainly =WILL= require
something more sophisticated than mere random delivery via passive "nanorods."
-- Gordon D. Pusch
perl -e '$_ = "gdpusch\@NO.xnet.SPAM.com\n"; s/NO\.//; s/SPAM\.//; print;' |
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| Manfred Bartz |
| Posted: Sat Oct 18, 2003 1:36 am |
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manofsan@yahoo.com (sanman) writes:
Hmm...
What happens with those nano-rods after they have delivered their
payload? They don't keep lying around like asbestos fibers, or
piling up inside cells like on a junkyard, do they?
--
Manfred |
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| sanman |
| Posted: Sun Oct 19, 2003 6:47 pm |
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gdpusch@NO.xnet.SPAM.com (Gordon D. Pusch) wrote in message
news:<bmqgd705l3@enews4.newsguy.com>...
Quote: As attempts to use retorvirii to transfer gene have shown, it is =NOT=
sufficient to simply "deliver" genes to cells, since genes spliced in
at random locations in random cells are highly unlikely to be properly
regulated, and often result in cancer, or even death of the patient.
For gene therapy to become practical, we must develop _targeted_ gene
delivery mechanisms that will ensure that therapeutic genes are only spliced
into the correct locations in the patient's DNA, complete with any flanking
regulatory regions, and are only expressed in the correct types of somatic
cell.
(Alternatively, a complete gene complex might be delivered as a complete
"mini-chromosome" containing all the genes and control regions required to
fill in for the malfunctioning portions of the patient's own metabolism,
and including some sort of fail-safe mechanism that will cause it to
inactivate itself if it finds itself in the wrong type of cell.) While
this sort of "targeted" therapeutic gene delivery might not require fully
programmable drexlerian nanobots, it almost certainly =WILL= require
something more sophisticated than mere random delivery via passive "nanorods."
Hi, thanks for this response. I've been wondering about that myself --
location-specific insertion of genes vs inserting an entire
pre-fabricated genome into the nucleus -- which would be more
practical/achievable?
Seems to me that you'd have the most flexibility in
tailorizing/modifying the genome if you were to synthesize it in the
test tube, and then insert it whole into the nucleus. You could do
your genetic manipulation/modification on the computer screen, and
then have a gene-making machine spit out an entire set of chromosomes
from scratch.
Then you'd need some way to reliably insert all these ready-made
chromosomal sets into all the billions of cells in the adult body.
Perhaps some kind of nano-delivery vehicle could be used for this. You
would also need to be able to reliably wipe out all the pre-existing
genetic information.
Ouch! No easy task. How to get all this done without causing cancer
outbreaks, disruption of life-sustaining metabolism, etc. Still,
synthesizing the whole chromosome outside the body would seem more
practical than relying upon a patchwork of various gene insertions.
Digressing towards another aspect of life-extension, I was thinking
about the idea of the "Markov Chain". Remember how they taught us in
linear algebra that you can apply a transformation matrix that
eventually leads you into a steady state situation? Well, the genomic
equivalent of that is what immortality should be based upon, imho.
Our current genome is designed to grow us from a fetus into an old
person who expires. "Planned obsolescence," as they say in the
automotive manufacturing industry. What we need for immortality, is a
genome that is designed to maintain our physical morphology in a
steady state equilibrium situation. Number of cells born equals number
of cells that are dying or wearing out, at all locations in the body,
keeping everything as is.
I remember reading that a key problem with getting genes to activate
properly is 'imprinting' which occurs during fertilization/conception.
So immortality would require "fertilization"/"insemination" of every
single one of your adult somatic cells. Scientists haven't been able
to overcome this with even a single zygote, let alone doing it for a
whole mass of cells comprising an adult living organism. Also, when a
sperm inseminates a zygote, a membrane change occurs which is supposed
to prevent other rival sperm from coming in and inseminating the same
zygote.
It's one thing to zap a single target which then multiplies into a
large number, but it's a whole lot messier to simultaneously and
reliably zap a large number of targets in a coordinated fashion. Talk
about 'immaculate conception'!
Can nano-delivery methods somehow bridge the gap? LOL, I know eyes
will roll for my saying it, but could quantum entanglement somehow
help? (ie. using quantum entanglement to coordinate the simultaneous
insemination of all the billions of somatic cells in an adult
organism?)
What do you think?
From a market economics point of view, it might be more realistic to
have certain industries pursuing R&D for specific tissue types
relating to their market niches. Cosmetics industry can focus on
improving longevity/youthfulness of the skin, hair, etc. Athletics
industries can focus on muscle, bone, connective tissues. Diet
industry can focus on keeping your gut from growing, and maintaining
youthful metabolic rates for proper fat-burning.
By dividing up the territory of the human body into niches, then you
don't have
solve it all in one shot.
In the end though, a comprehensive solution would require radically
modifying your existing genome into that steady state "Markov Chain"
genome that I mentioned.
And how about nanotech supplementing biological mechanisms -- people
could be implanted with tiny biochip devices that could release extra
nutrients or protective anti-oxidants or whatever, in response to
certain events or environmental changes. People would always be
assured of getting exactly the nutrition they needed, at all times. |
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| Bob |
| Posted: Tue Nov 04, 2003 11:23 am |
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On 18 Oct 2003 04:43:19 GMT, gdpusch@NO.xnet.SPAM.com (Gordon D.
Pusch) wrote:
Quote:
manofsan@yahoo.com (sanman) writes:
Nano-rods have been used to deliver genes:
http://www.nanotechweb.org/articles/news/2/10/10/1
Hey, maybe this will be the real means by which nano-technology will
extend our lifespans, rather than the nanobots.
As attempts to use retorvirii to transfer gene have shown, it is =NOT=
sufficient to simply "deliver" genes to cells, since genes spliced in
at random locations in random cells are highly unlikely to be properly
regulated, and often result in cancer, or even death of the patient.
For gene therapy to become practical, we must develop _targeted_ gene
delivery mechanisms that will ensure that therapeutic genes are only spliced
into the correct locations in the patient's DNA, complete with any flanking
regulatory regions, and are only expressed in the correct types of somatic
cell.
(Alternatively, a complete gene complex might be delivered as a complete
"mini-chromosome" containing all the genes and control regions required to
fill in for the malfunctioning portions of the patient's own metabolism,
and including some sort of fail-safe mechanism that will cause it to
inactivate itself if it finds itself in the wrong type of cell.) While
this sort of "targeted" therapeutic gene delivery might not require fully
programmable drexlerian nanobots, it almost certainly =WILL= require
something more sophisticated than mere random delivery via passive "nanorods."
I finally got around to reading the article that is the basis of this
news item. It is in Nature Materials 2:668, Oct 03.
This is for non-viral gene delivery. With non-viral gene delivery, the
intent is that the gene stays only for a short time. The problem
alluded to above (with retroviruses) is not with regulation but with
"improper" integration. With non-viral DNA delivery, it is not
integrated at all. Such transient gene expression may be relevant for
use of DNA as a vaccine, as well as for some types of therapeutic
treatment. This form of gene treatment should not be confused with the
type that leads to a permanent addition of a gene.
What they did here was to use a bi-metallic "nanorod", and they worked
out a method to attach DNA to one metal and a cell-targeting protein
to the other. The data they show suggest this has promise -- though of
course any such initial report must be taken as only a hint.
As to viral gene delivery... the virus is used to get recombination
into the genome. These systems typically provide something like random
integration -- though it isn't really random.
We should not over-react to the problems with the gene therapy trial
for X-SCID that is in progress. 10 youngsters with an inevitably fatal
disease were treated with the retroviral gene therapy. Nine seem to
have achieved a cure. Two of those have developed a leukemia, which
was treatable. Of course, we do not know whether more will. But at
this point, even with the side effect, the treatment must be
considered successful. "Cure rate" is high, and side effects are
"minor" -- compared to the disease being treated.
The reasons for the leukemia development are being analyzed, and
frankly are still confusing. Clearly the virus integrated in a "bad"
location; in that sense it is understood what happened. But there must
be more to the story, as side effects with this type of viral delivery
are actually less frequent than one would expect.
bob |
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