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Could this be a possible treatment for HIV/AIDS?

 
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douglas
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PostPosted: Fri May 09, 2008 9:06 pm    Post subject: Could this be a possible treatment for HIV/AIDS? Reply with quote

Could this be a possible treatment for HIV/AIDS:

Synthesize a peptide nucleic acid antisense oligonucleotide for HIV’s
gag gene’s mRNA. The reason for using PNA is that it is substantially
more resistant to enzyme degradation by nucleases and proteases. The
reason for choosing the gag gene is that it’s proteins, p24, p17, p7,
and p6, code for the basic physical infrastructure of HIV; w/o these
key proteins, there is no HIV. Then, encapsulate the oligonucleotides
in liposomes studded w/ anti-CD4 antibodies. This will ensure 1)
toxicity is limited—cf Ambisome, the liposomal preperation of
amphotericin B—2) the biologic goes only where it’s needed, which is
the cytoplasm of CD4+ T-cells. Decorating the liposome w/ anti-CD4
antibodies will trigger endocytosis, in my limited knowledge, at
least. I predict low toxicity and high efficacy in reducing the
patient’s viral load to hopefully 0 copies/ml.

Maybe, when I'm doing my PhD or MD dissertation --a long ways off, see
below--, I could do it on this, patent the resulting product --ie the
PNA oligonucleotide itself--, and license it to Genentech or Hybridon
for further development into a marketable biologic.

What are your thoughts? Should LNA instead of PNA be used? Cell-
penetrating peptides vs. liposomes? Targeting the gag gene vs.
targeting the pol gene? Are there any publications about this subject?
And, just for fun, what do you think the generic name would be for
this biologic? Brand name?

BTW, if this helps you answer, I'm a 16.5 year old community college
freshman who hopes to have a career as a physician-scientist.

Thanks!!!!
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douglas
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PostPosted: Sat May 10, 2008 6:49 pm    Post subject: Re: Could this be a possible treatment for HIV/AIDS? Reply with quote

On May 10, 7:46 am, "N10" <limbic_les...@hotmail.com> wrote:
Quote:
Your future is assured, this a brilliant idea for one so young.

N10"douglas" <Protoman2...@gmail.com> wrote in message

news:dce0208f-8fac-4ba3-8310-f6cfcd700d51@b5g2000pri.googlegroups.com...
Could this be a possible treatment for HIV/AIDS:

Synthesize a peptide nucleic acid antisense oligonucleotide for HIV’s
gag gene’s mRNA. The reason for using PNA is that it is substantially
more resistant to enzyme degradation by nucleases and proteases. The
reason for choosing the gag gene is that it’s proteins, p24, p17, p7,
and p6, code for the basic physical infrastructure of HIV; w/o these
key proteins, there is no HIV. Then, encapsulate the oligonucleotides
in liposomes studded w/ anti-CD4 antibodies. This will ensure 1)
toxicity is limited—cf Ambisome, the liposomal preperation of
amphotericin B—2) the biologic goes only where it’s needed, which is
the cytoplasm of CD4+ T-cells. Decorating the liposome w/ anti-CD4
antibodies will trigger endocytosis, in my limited knowledge, at
least. I predict low toxicity and high efficacy in reducing the
patient’s viral load to hopefully 0 copies/ml.

Maybe, when I'm doing my PhD or MD dissertation --a long ways off, see
below--, I could do it on this, patent the resulting product --ie the
PNA oligonucleotide itself--, and license it to Genentech or Hybridon
for further development into a marketable biologic.

What are your thoughts? Should LNA instead of PNA be used? Cell-
penetrating peptides vs. liposomes? Targeting the gag gene vs.
targeting the pol gene? Are there any publications about this subject?
And, just for fun, what do you think the generic name would be for
this biologic? Brand name?

BTW, if this helps you answer, I'm a 16.5 year old community college
freshman who hopes to have a career as a physician-scientist.

Thanks!!!!

That's nice!!! But what about the actual idea itself?
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N10
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PostPosted: Sat May 10, 2008 7:46 pm    Post subject: Re: Could this be a possible treatment for HIV/AIDS? Reply with quote

Your future is assured, this a brilliant idea for one so young.


N10
"douglas" <Protoman2050@gmail.com> wrote in message
news:dce0208f-8fac-4ba3-8310-f6cfcd700d51@b5g2000pri.googlegroups.com...
Could this be a possible treatment for HIV/AIDS:

Synthesize a peptide nucleic acid antisense oligonucleotide for HIV’s
gag gene’s mRNA. The reason for using PNA is that it is substantially
more resistant to enzyme degradation by nucleases and proteases. The
reason for choosing the gag gene is that it’s proteins, p24, p17, p7,
and p6, code for the basic physical infrastructure of HIV; w/o these
key proteins, there is no HIV. Then, encapsulate the oligonucleotides
in liposomes studded w/ anti-CD4 antibodies. This will ensure 1)
toxicity is limited—cf Ambisome, the liposomal preperation of
amphotericin B—2) the biologic goes only where it’s needed, which is
the cytoplasm of CD4+ T-cells. Decorating the liposome w/ anti-CD4
antibodies will trigger endocytosis, in my limited knowledge, at
least. I predict low toxicity and high efficacy in reducing the
patient’s viral load to hopefully 0 copies/ml.

Maybe, when I'm doing my PhD or MD dissertation --a long ways off, see
below--, I could do it on this, patent the resulting product --ie the
PNA oligonucleotide itself--, and license it to Genentech or Hybridon
for further development into a marketable biologic.

What are your thoughts? Should LNA instead of PNA be used? Cell-
penetrating peptides vs. liposomes? Targeting the gag gene vs.
targeting the pol gene? Are there any publications about this subject?
And, just for fun, what do you think the generic name would be for
this biologic? Brand name?

BTW, if this helps you answer, I'm a 16.5 year old community college
freshman who hopes to have a career as a physician-scientist.

Thanks!!!!
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douglas
Guest





PostPosted: Sun May 11, 2008 8:01 pm    Post subject: Re: Could this be a possible treatment for HIV/AIDS? Reply with quote

On May 11, 11:40 am, Joachim Pimiskern <JoachimPimisk...@web.de>
wrote:
Quote:
douglas schrieb:
 > The reason for choosing the gag gene is that it’s proteins,
 > p24, p17, p7, and p6, code for the basic physical infrastructure
 > of HIV; w/o these key proteins, there is no HIV.

I'm not a microbiologist, but happened to bookmark these links:http://www.eurekalert.org/pub_releases/2006-12/mgh-ehc121406.phphttp://www.eurekalert.org/pub_releases/2006-12/wt-qnq121406.php

Regards,
Joachim

So targeting gag is important. But those articles were talking about
inducing an CD8+ T-cell response to gag, and destroying infected CD4+
T-cells. Based on those articles' logic, we might as well use an anti-
CD28 mAb linked to an anti-CD4 mAb --http://en.wikipedia.org/wiki/
TGN1412 for an analogy to what effect this should cause--. That'll be
"entertaining".

What about studding the liposome w/ anti-gp120 mTcRs --http://
en.wikipedia.org/wiki/Artificial_T_cell_receptor--? Then the drug'll
be delivered to all cells infected w/ HIV, not just CD4+ ones.

Here's another possible anti-HIV biologic: synthesize an anti-gp160
mTcR linked to caspase-3 --or something that'll result in an apoptosis
signal be transmitted, like DISC, or FasR...cell signalling confuses
me--, which should induce the apoptosis of any cell which contains the
HIV protein gp160. I'm not so good w/ mTcRs and cell signalling, could
you guys help explain more fully exactly what an mTcR does? I know
it's an artificial T-cell receptor, and it modifies the responses of T-
cells, but beyond that...

Thanks!!!
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Joachim Pimiskern
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PostPosted: Sun May 11, 2008 11:40 pm    Post subject: Re: Could this be a possible treatment for HIV/AIDS? Reply with quote

douglas schrieb:
Quote:
The reason for choosing the gag gene is that it’s proteins,
p24, p17, p7, and p6, code for the basic physical infrastructure
of HIV; w/o these key proteins, there is no HIV.

I'm not a microbiologist, but happened to bookmark these links:
http://www.eurekalert.org/pub_releases/2006-12/mgh-ehc121406.php
http://www.eurekalert.org/pub_releases/2006-12/wt-qnq121406.php

Regards,
Joachim
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Joachim Pimiskern
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PostPosted: Fri May 16, 2008 10:38 am    Post subject: Re: Could this be a possible treatment for HIV/AIDS? Reply with quote

douglas schrieb:
Quote:
What about studding the liposome w/ anti-gp120 mTcRs --http://
en.wikipedia.org/wiki/Artificial_T_cell_receptor--? Then the drug'll
be delivered to all cells infected w/ HIV, not just CD4+ ones.

As you mention gp120 and CD4 - David Baltimore wants
to design an artificial antibody for gp120.

http://www.google.com/search?hl=de&q=David+Baltimore+gp120+cd4

Regards,
Joachim
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douglas
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PostPosted: Fri May 16, 2008 11:05 pm    Post subject: Re: Could this be a possible treatment for HIV/AIDS? Reply with quote

On May 15, 10:38 pm, Joachim Pimiskern <JoachimPimisk...@web.de>
wrote:
Quote:
douglas schrieb:

What about studding the liposome w/ anti-gp120 mTcRs --http://
en.wikipedia.org/wiki/Artificial_T_cell_receptor--? Then the drug'll
be delivered to all cells infected w/ HIV, not just CD4+ ones.

As you mention gp120 and CD4 - David Baltimore wants
to design an artificial antibody for gp120.

http://www.google.com/search?hl=de&q=David+Baltimore+gp120+cd4

Regards,
Joachim

Hmmm. But it won't destroy the infected cells that hide during
treatment, only 10-15%. That's why we need mTCRs
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