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Science

Tailor-Made Cancer Drugs 17

pmineiro writes "A researcher at Washington University in St. Louis has developed a method for delivering an inactive drug complex into the body, which is only activated by certain messenger RNA sequences. This allows a drug to be selectively activated only in certain cellular contexts, e.g., cancer or HIV infection."
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Tailor-Made Cancer Drugs

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  • First Post (Score:1, Offtopic)

    This is very interesting. Any other electrical engineers out there wish they had a biology background when they read stuff like this?
  • by tps12 ( 105590 )
    At first this sounds like a miracle drug. You inject it into everybody, and it only starts working when there's a problem. But it's pretty obvious that this is just an accident waiting to happen.

    In the presence of cosmic rays and background radiation, to say nothing of the computer monitors, cellular phones, and irradicated beef that we surround ourselves with every day, these genetic superdrugs could easily mutate. In their new forms, they'd be essentially unstoppable. One stray gramma ray could spell the end of humanity.

    I'd like to fight cancer and HIV as much as anyone else. But I'll stick to traditional means, rather than meddling where Nature never intended.
    • So only give it to people known to have the disease it fights.
    • That doesn't seem to be how it works. You would have to biopsy the specific cancer that you are trying to destroy to get the correct trigger sequence. Attacking a virus may be more generic, but I doubt this could be used as a preventative measure. This seems to be much more useful as an after-the-fact cure. If I had cancer or HIV I would definitely grab this in an instant. Chemo can be pretty effective, but it does a lot of damage to healthy tissue as well. This seems like the ideal way to avoid that.

      -SablKnight
    • by helix400 ( 558178 ) on Tuesday October 29, 2002 @04:24PM (#4558494) Journal
      In the presence of cosmic rays and background radiation, to say nothing of the computer monitors, cellular phones, and irradicated beef that we surround ourselves with every day, these genetic superdrugs could easily mutate. In their new forms, they'd be essentially unstoppable. One stray gramma ray could spell the end of humanity.

      You would make a great B-Movie script writer.
      Unfortunately, virtually nothing you said can be backed up scientifically. Your flaws are these:

      1) How is this drug going to spread? Drugs are molecules, not viruses or bacteria. The drug will simply stay inside the person they give it to.
      2) If this drug *could* spread, how is it going to reproduce itself? Luckily, drugs dont self-divide or mate to reproduce.
      3) Irratiated beef is NOT radioactive, neither are cell phones. Therefore, harmless beef and cell phones will not alter a drug. (Techinically cell phones give off radiation in the form of radio waves, but visible light gives off far more energetic radiation than a cell phone does.)
      4) Gamma rays, computer monitors, and background radiation could only affect a change in the drug in miniscule amounts. Generally, if one drug molecule was hit by a stray gamma ray, it would change one molecular bond, and perhaps mess up the configuration of the molecule. At absolute worst, a single change alter the drug in such a way that it would kill the person using the drug, but that's *extremely* unlikely.

      Personally, I've read the article, and feel this is a pretty good idea. He uses already approved FDA drugs, and just does a better job targeting them.

      ---
      Abortions for some, miniature American flags for others! - Kodos

    • Think of it as cryptology. You have a PGP encoded message (drug) that can only be unlocked by the appropriate key (rna trigger).

      Your cosmic ray scrambles the code, and the odds of it binding to some random spot is low. How low? That would be good to know.

      But the whole dru/key pairing is artificial, it does not reproduce, so even if the one molecule of the batch they give you for disease X gets scrambled, you are the only one who has to worry, and in fact, it is only one healthy cell that has to worry, because once that molecule delivers its payload, no more payload.

      So, in this case, sleep well, for humaity is safe.

      You may want to avoid Porktatos, the latest GMO snack, however...};^)
    • by idiot900 ( 166952 ) on Tuesday October 29, 2002 @05:35PM (#4559137)
      > In the presence of cosmic rays and background
      > radiation, to say nothing of the computer
      > monitors, cellular phones, and irradicated beef
      > that we surround ourselves with every day, these
      > genetic superdrugs could easily mutate. In their
      > new forms, they'd be essentially unstoppable.
      > One stray gramma ray could spell the end of
      > humanity.

      <SARCASM>So, good thing you actually read the article, and have a solid grasp of the relevant biology.</SARCASM>

      Mutations in the prodrug and catalyst would most likely decrease their binding affinity for their target sequence, and likely mRNA sequence in general. Thus, the drug would be *less* likely to be activated.

      The idea that the "genetic superdrugs" would easily mutate and "spell the end of humanity" is ludicrous. For this to happen, they would need some way to reproduce themselves, which they don't. If they did, they would be analogous to virii. While virii are often pathogenic, they haven't destroyed humanity as of yet.

      (By the way, I'm amused by people who talk about "what Nature intended". Did you have a nice long chat with Nature about this stuff? Did Nature give you an itemized list of things Nature intended? If so, the next time you and Nature do lunch, I'd like to tag along.)
      • As I see it, the whole thing won't work on a broad scale anyway without a great deal of rather expensive personalization of the drugs.

        Because of the redundancies of the genetic code, even highly conserved nucleic acid sequences likely differ significantly between individuals (don't forget also that a single gene mutates on average every million replications, each person has trillions of cells, many of which live a short period, then replicate themselves and their entire genome).

        Secondly, cancer cells are highly mutated from their original form, and barely hang on to life as they replicate as fast as they can. They are probably not very representative of the person that they originate in.

        The result is that the drugs will likely need to be adapted to work in every patient specifically, will need to be synthesized, purified, possibly isolated from their isomers, etc.... It's not that this isn't feasible, but I don't see it as being able to be effectively provided as of yet.
        • by mik ( 10986 )
          As I see it, the whole thing won't work on a broad scale anyway without a great deal of rather expensive personalization of the drugs.

          Do you have any idea what "traditional" cancer treatment costs?!? I got about (US) $30K of radiation treatments in one month and I'm pretty sure that 6 months of chemotherapy wasn't exactly cheap. Add in surgery and my personal bill surely tops $60K.

          With custom full sequencing coming down in price (see Race for the $1000 genome is on [newscientist.com] for instance), such custom tailoring of drugs doesn't seem so ridiculous any more.

  • This is big (Score:3, Insightful)

    by Henry V .009 ( 518000 ) on Tuesday October 29, 2002 @03:43PM (#4558086) Journal
    Very cool. The very generalness and nature of this approach makes me want to categorize this as nano-machine rather than new drug.
  • Scary (Score:3, Interesting)

    by Rick the Red ( 307103 ) <Rick.The.Red@nOsPaM.gmail.com> on Tuesday October 29, 2002 @03:45PM (#4558101) Journal
    Maybe I've got an evil side that sees the bad in things, but this reminds me of several stories where individuals are targeted based on their DNA. Seems like a small step from this to a poison that only activates in people with a specific DNA sequence...

    • Re:Scary (Score:1, Funny)

      by joto ( 134244 )
      Yup. It would be the most efficient way of eradicating jews forever. As we all know, jews are a matrilineal society, and thus they all share some common genes.

      I only wish Hitler was still alive to see his dream come true.

      (Yes, this is a joke...)

  • It was back in the late nineties I first heard about using PNA as a targeting mechanism for so called "magic bullets". Does anybody know what is new about this story? The major problems were stability of PNAs in the body and actually getting it to the right place, if I recall correctly.

    • Check out this site here and read up on Morpholinos [morpholino.com]. The news release is a little too dumbed-down to be much use (and didn't cite any references), but this is pretty much the same thing. Most morpholinos need to be injected directly into the cell, at least to be effective for what they're being used for (gene knockdowns, etc), but liposome or other delivery mechanisms could easily be developed to deliver them via inhalation, injection, pills, whatever. These only bind to single-stranded RNAs, so there's no worry of interfering with DNA. They are fairly stable, phenotypes can be rescued, quite cheap, and easy to work with.
  • by Anonymous Coward
    it's a shame that technology that makes such good medicine (for obvious reasons) also makes such good weapons. That could be used to "target anybody with blue eyes" or "target anybody with curly hair", etc etc. History doesn't need repeating.

"Protozoa are small, and bacteria are small, but viruses are smaller than the both put together."

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