[net.med] attacking viruses

phil@amdcad.UUCP (Phil Ngai) (08/13/85)

Recently someone commented that modern medicine can do little against
illness caused by viruses. I had a thought which goes like this:
in recombinant DNA research they use agents (a form of RNA?) which
cut the genes at precise points. Then other methods are used to splice
together the pieces as desired. Could we simply employ the right agents
to cut up the genes in nasty viruses? I realize they are carried in
protein containers and the genes are directly injected into the victim
cells. But I wanted to throw out this idea. The cutting agents seem
to be programmed to cut at precise places, which means they should be
able to attack the desired virus and nothing else. Or I could be all wet.
I'm an engineer, not a doctor.
-- 
 Yuck! This coke tastes different!

 Phil Ngai (408) 749-5720
 UUCP: {ucbvax,decwrl,ihnp4,allegra}!amdcad!phil
 ARPA: amdcad!phil@decwrl.ARPA

roy@phri.UUCP (Roy Smith) (08/14/85)

Phil Ngai <amdcad!phil> says:
> in recombinant DNA research they use agents (a form of RNA?) which cut the
> genes at precise points. [...]  Could we simply employ the right agents to
> cut up the genes in nasty viruses? [...] The cutting agents seem to be
> programmed to cut at precise places, which means they should be able to
> attack the desired virus and nothing else.

	The agents are called restriction endonucleases or, more commonly
restriction enzymes, and are made of protein, not rna.  This detail aside,
they do indeed cut at precise places; the accuracy with which they find
their proper cut sites and reject all others is staggering.  Because of
this, you can use them to cut-and-paste dna in the lab using them as the
scissors.  It's hard to imagine *anything* being done in a molecular biology
lab without them.

	These enzymes exist for exactly the reason you want to use them as
therapeutic agents.  Certain bacteria make restriction enzymes which are
programmed to cut dna at nucleotide sequences which don't appear at all in
that species' own dna.  Thus, the bacteria are immune from being turned into
dna salad by their own enzymes.  However, when foreign dna gets into the
cell, as happens when under attack by a virus, the enzymes go to work and
chop it up.  The concept is similar to making antibodies, though the
mechanisms are totally different.

	There are lot of problems, however, with using restriction enzymes
to treat viral infections in people.  First you would have to find a way to
get them into the body.  Orally won't work because they won't survive being
in the digestive system long enough to be absorbed.  I have no idea what
would happen if you administered them I.V. or I.M. -- Craig, care to take
this one?  Even if you got them where they had to go, you need the right
conditions of salt, pH, etc to work right.

	Those problems are trivial compared to the fact that we can't
program these enzymes ourselves (at least not yet).  All we can do is use
the ones that bacteria are kind enough to make for us.  To engineer a
restriction enzyme which would specifically attack viruses (or even just one
particular virus) while leaving our own dna alone is way beyond our current
technology.

> I'm an engineer, not a doctor.

	That's OK.  Us engineers are smarter than doctors anyway.  We just
don't make as much money.
-- 
Roy Smith <allegra!phri!roy>
System Administrator, Public Health Research Institute
455 First Avenue, New York, NY 10016

roy@phri.UUCP (Roy Smith) (08/14/85)

	Since the topics seem to have drifted to molecular biology, I
thought I should point out a good reference, written for use in an
undergraduate introductory course in biochemistry and molecular biology.

%A James D. Watson
%T Molecular Biology of the Gene, Third Edition
%E W. A. Benjamin, Inc
%C Menlo Park, California
%O ISBN 0-8053-9609-8
-- 
Roy Smith <allegra!phri!roy>
System Administrator, Public Health Research Institute
455 First Avenue, New York, NY 10016

gnome@olivee.UUCP (Gary Traveis) (08/15/85)

> Recently someone commented that modern medicine can do little against
> illness caused by viruses. I had a thought which goes like this:
> in recombinant DNA research they use agents (a form of RNA?) which
> cut the genes at precise points. Then other methods are used to splice
> together the pieces as desired. Could we simply employ the right agents
> to cut up the genes in nasty viruses? I realize they are carried in
...

Any agent that is that powerful would do a job on everything else
in your body.

There is a drug that is used to slow down the spreading of viral
infections.  In it's early stages, influenza can be kept from
multiplying by the introduction of Amantadine.  This drug keeps
the virus from breaking through cell walls, and therefore making
new DNA material.  It doesn't help if your body has been overrun
with 'flu but does give your body time to build up antibodies
(as compared to having your metabolism screwed-up to the point
of no return).

Like I said, it is only useful for people that can tell when
they are initially coming down with the flu.  If you ignore it
until it lays you out, Amantadine won't help.

Gary
(hplabs,allegra,ihnp4)oliveb!olivee!gnome

werner@aecom.UUCP (Craig Werner) (08/20/85)

> Phil Ngai <amdcad!phil> says:
> > in recombinant DNA research they use agents (a form of RNA?) which cut the
> > genes at precise points. [...]  Could we simply employ the right agents to
> > cut up the genes in nasty viruses? [...] The cutting agents seem to be
> > programmed to cut at precise places, which means they should be able to
> > attack the desired virus and nothing else.
> 
> 						Craig, care to take this one?  
> 	Roy Smith <allegra!phri!roy>

	Actually I already mailed a response, but with a lead-in like that, I
couldn't turn it down.
	Restriction Enzymes, as described above, generally cut at pre-defined
sequences of usually 6 DNA bases, usually palinodromic (2-fold symetrical).
However, since DNA has only four bases total, the odds of coming up with a
recognition site just by random chance occurs about once every gene or two,
so there is no way to make them specific for viral sequences. (The bacteria
they come from skirt this problem by modifying their own DNA, so only newly
introduced foreign DNA is snipped. Human cells don't do this.)
	Besides, the restriction enzymes are proteins (not RNA, as Phil 
guessed), and proteins cannot get into cells. Protein Hormones get around
this by using receptors, but human cells cannot be expected to have receptors
for bacterial proteins.
	Hence, they would never get to the viral DNA, and even if they did,
they would cut too much of the cellular DNA in the process.
	As Phil said in his response to me, "Oh, well, it was a good idea..."

-- 
				Craig Werner
				!philabs!aecom!werner
		"The world is just a straight man for you sometimes"