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

[marcus]

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..."

 

[Ryan_m_b]

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.

 

[marcus]

...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

 

[Ryan_m_b]

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).

 

[Ygggdrasil]

We've discussed this paper in the Biology subforum as well. See the following thread for my thoughts on the DRACO approach:

https://www.physicsforums.com/showthread.php?t=521168

 

[Ygggdrasil]

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.