Smart new antiviral concept-DRACO at MIT Lincoln Lab-Todd Rider

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Discussion Overview

The discussion centers around the DRACO antiviral concept developed at MIT Lincoln Lab, focusing on its potential efficacy, mechanisms, and implications for viral treatment. Participants explore the theoretical and practical aspects of DRACO, including its application in vivo, evolutionary considerations, and comparisons to existing antiviral strategies.

Discussion Character

  • Exploratory
  • Technical explanation
  • Debate/contested

Main Points Raised

  • Some participants express caution regarding the indiscriminate targeting of all active viruses by DRACO, raising concerns about the potential impact on beneficial viruses.
  • Others highlight the innovative approach of targeting longer RNA found in viruses, suggesting it could outperform current treatments like interferons.
  • Concerns are raised about the long-term viability of DRACO due to evolutionary pressures that may lead to resistance or unintended consequences.
  • A participant notes the importance of timing in administering DRACO, as its effectiveness may be compromised if given after infection has progressed significantly.
  • There is a discussion about the limitations of DRACO in terms of its short-lived effects in the body compared to vaccines, which provide longer-lasting immunity.
  • Some participants reference related discussions in other forums and analyses that provide additional insights into the DRACO approach and its challenges.

Areas of Agreement / Disagreement

Participants generally agree on the innovative nature of the DRACO concept but express differing views on its potential effectiveness, the implications of its mechanism, and the challenges it faces in practical application. There is no consensus on the long-term viability or safety of the approach.

Contextual Notes

Participants note the need for further research to address the evolutionary dynamics that could affect the efficacy of DRACO and the timing of its administration in relation to viral infection.

marcus
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Smart new antiviral concept--DRACO at MIT Lincoln Lab--Todd Rider

http://web.mit.edu/newsoffice/2011/antiviral-0810.html

Have to see if the concept can actually work in vivo. There could be some catch. One catch could arise if there are "good" viruses we actually need to be active, or some pervasive harmless type. Because the treatment concept seems to go after all active viruses indiscriminately. It causes the host cell to self-destruct wherever double-stranded RNA is being produced (dsRNA is produced during viral replication).

Looks good in vitro and preliminary trials in mice but has not been tried in larger animals. Here's a link to some PR about Todd Rider and Lincoln Lab.
http://www.ll.mit.edu/60thAnniversary/rider.html

"Rider had the idea to combine a dsRNA-binding protein with another protein that induces cells to undergo apoptosis (programmed cell suicide) — launched, for example, when a cell determines it is en route to becoming cancerous. Therefore, when one end of the DRACO binds to dsRNA, it signals the other end of the DRACO to initiate cell suicide..."
 
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When I read this research it really raised an eyebrow. But it's a neat idea, targeting the longer RNA found in viruses. It would be great if this could be the next (but better) interferon but I worry that without other research in conjunction one day this will fail as evolution takes it's course.
 


ryan_m_b said:
...without other research in conjunction one day this will fail as evolution takes it's course.

Yes! Evolution does invariably take its course. Sooner or later nature circumvents you or you discover unintended consequences of your bright idea. But it seems like a bold attempt so I'll be rooting for them.

They published in a free online journal, which was nice of them. Here is the PLoS link:
http://www.plosone.org/article/info:doi/10.1371/journal.pone.0022572
 


marcus said:
Yes! Evolution does invariably take its course. Sooner or later nature circumvents you or you discover unintended consequences of your bright idea.

Indeed, this is why http://en.wikipedia.org/wiki/New_Delhi_metallo-beta-lactamase_1" scares me. Specifically the disturbing lack of political will to address the danger of antibiotic resistance (especially the danger of sudden mass adoption through horizontal transfer).
 
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Here's another nice analysis about the paper (http://pipeline.corante.com/archives/2011/08/22/dracos_new_antivirals_against_pretty_much_everything.php ) that brings up a few new points:
You might have already wondered about my mention of the injection route, since we already give millions of people a year injections to combat viral infection: flu shots. Those, though, are vaccines meant to last the whole season (and beyond). DRACO proteins get cleared out in mice on a time scale of days; they wouldn't be expected to have any long-range immune effects. (Of course, their broad antiviral effects, versus the sometimes way-too-specific nature of a vaccine, is a strong point in their favor). But this brings up another issue that's going to have to be addressed: when you look at the graphs of the mice experiments, you note that the DRACOs were given either on Day 0 or Day -1 compared to the exposure to virus.

That's actually a big deal in this field. The problem with antiviral therapies has always been that you don't usually know that you've been infected until, well, after you've been infected. Sometimes that lag time is rather long, and it's always long enough for the virus to get a good running start. Symptoms, after all, don't occur until things are well under way. In the real world, the two opportunities for antiviral therapies are (1) something that you can take long before you're even exposed, and that lasts for a long time (like a vaccine) or (2) something that you can take after you've already realized that you're sick (like an antiviral drug). So far, the DRACO proteins fall in between these two, and the next challenge for these agents is to see if they can stretch into one or the other.

Because these agents work by killing infected host cells, applying these agents to someone who has already been infected may produce unacceptable levels of cell death and may not actually be effective in helping the patient.
 
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