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twilyth
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RNA discussion thread

"Are you sure you know what you're talking about. You're implying that the siRNA's are derived from piRNA's when the 2 are well know to be completely separate classes"

I should have worded the previous statement as piRNA's are analagous in their overall function to that of RNAi in that they both elicit silencing. I did not however, imply that siRNA are derived from piRNA's. All this being said, I"m done explaining myself on this. If you want to chat about it on another thread or in a PM that's fine.


Getting back to the RNA immunization article, it was interesting and of potential value. They did some important experiments, including testing the ability of the RNA to elicit a response in young and adult mice.

That being said, the authors waited only 5 weeks after the last administration of RNA before challenging the mice with influenza. I would wonder whether their results were due in part to activating either long lived and/or effector memory cells instead of central memory cells.

Other things to think about. While RNA can be made encoding a ton of different viral proteins, is it such a good thing to have memory T and B cells directed against all of those proteins? There has been at least one set of publications where sequential challenges of mice changed the composition of the memory T cell pool with each infection. There were less of the primary virus specific memory T cells.

In addition, there is also a question to whether using a shotgun RNA immunization strategy might also lead to an increase in autoimmune diseases due to activation of previously anergic and autoreactive T cells, either indirectly or by molecular mimicry and direct TCR stimulation.

If you didn't mean imply that piRNA were the source, the what exactly were you saying was unstable?

As to your criticisms of the article, the existence of effector memory cells by definition implies that they would have been challenged with virus previously. I'm pretty sure that would have been a violation of the test protocol so I'm not sure how you came up with that.

I'd like to see a cite for the claim that t-cell population declines with repeated challenges - unless that is due to a compromised immune system due to excessive stress.

As to the activation of autoreactive T-cells, these are normally destroyed early in development. Since the mRNA codes for viral proteins an since in a murine model it appears that the exogenous mRNA is absorbed and transcribe into viral proteins, it seems about as likely to cause and autoimmune response as a flu shot.
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