Feedback on a Draft

[Shin jie Yong]

Dear all, 

I am a neurobiology MSc postgraduate student who is actively writing blog posts about coronavirus. This mRNA discussion group has been very helpful in helping me understand more about the topic, so I am very much honored to be a member. 

I have here an unpublished draft about mRNA vaccine and lipid nanoparticles. I plan to publish it sometime next week. So, in the meantime, I would appreciate any feedback or further discussion from anyone here, if you have any. 

I have incorporated a few of the links Dr. Stewart has posted in this group, as well as an email discussion I had with Dr. Goh. I am still waiting for a response from Dr. Ulm for permission to quote his comments. Thus, I have thanked and mentioned your names at the end of the draft, but please let me know if it makes you uncomfortable. 

Kind regards,

Shin Jie Yong

[Wm. Stewart]

Hi Shin, I think this is one of the most balanced and thorough reviews of a very complex subject that I have seen.  Congratulations. 

Good work.

Bill

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[Shaw, Christopher]

thanks.

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Sent: March 4, 2021 1:06:46 PM
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Subject: Re: [mRNAdiscuss] Feedback on a Draft

 

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[Shaw, Christopher]

And we can all speculate forever, but someone has to get some funds and do the basic experiment with the mice again, with a longitudinal study, the appropriate behavioural and histological analysis within the CNS, etc. 

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From: mrnad...@googlegroups.com <mrnad...@googlegroups.com> on behalf of Shin jie Yong <shinj...@gmail.com>
Sent: March 4, 2021 7:23:29 AM
To: mrnadiscuss
Subject: [mRNAdiscuss] Feedback on a Draft

 

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[J. Wes Ulm, MD, PhD]

100% agreed, this was my sense amid that discussion on the Sciencemag blog, as productive as it was, we were all stuck in varying degrees of educated conjecture due to the sheer paucity of data on the tissue localization question. Also the in vivo studies on tissue trafficking, deposition, and cytotoxicity would have to utilize the exact LNP formulation and encapsulation as used in the vaccines in public use; this was another source of confusion in prior discussions, simply because LNP formulations differ so markedly from each other in their character and in vivo behavior. Oh this point, as I understand it, Pfizer and Moderna have both been stating that their LNP formulations are proprietary trade secrets and have not been fully disclosed publicly (at least not in a way that would allow their faithful reproduction), apparently still concerned about each other poaching the formula, which has been a headache for a lot of independent analysis and I'm not sure offhand how to overcome it practically speaking. Might be something that the medicines agencies in different countries/regions might have to coordinate.

Wes

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[Shaw, Christopher]

I agree. Proprietary or not, someone could buy the vaccine, scale it down to mouse volume by weight, inject and follow over an extended time course. Lots of labs could do the behaviour and histology: behaviour over a course of months, maybe different sexes and ages (a lot more money), do histology of brain including mRNA and or construct analysis for various regions, histology for the construct in various brain regions over time, measure markers of inflammation, cell death etc. etc. All do-able. Not even that costly...couple hundred $K.  Does it prove the same happens in humans: for sure not, but at least we'd have some clue on what might be happening. And, if se saw something disturbing, at least we might get some advance warning of what might be coming...or, we'd find that it is likely all OK.  Might be worth the money to know either way. However, since vaccine stuff is extremely polarized, I can't see NIH or other entities funding this. However, a corollary is to ask what happens with the natural viral infection since some of the symptoms of Covid-19 positive humans look a lot like neural impacts...do that in ferrets? 

 

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From: J. Wes Ulm, MD, PhD <wes...@post.harvard.edu>
Sent: March 4, 2021 6:34:46 PM
To: Shaw, Christopher
Cc: Shin jie Yong; mrnadiscuss
Subject: Re: [mRNAdiscuss] Feedback on a Draft