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Native Answers Coronavirus Related Basic Science Questions

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Native

ToungeInCheek since 2010
Staff member
10 Year Member
From another thread I got drug into.... but has some info I want to have placed here on the development of mRNA vaccines.

Here is the link to the review.. https://www.nature.com/articles/nrd.2017.243#Sec5
(I wouldn't likely attempt to read this unless you have a science background.)

Distilled TL-DR of an aspect of the review. (Bolded bullet in Box 1)

So basically our immune system has some innate capabilities to recognize some foreign structures as foreign without having to go through adaptive immunity. This allows for immediate generalized detection of a lot of bacteria, and viruses. These receptors are called Toll-Like receptors and are numbered 1-10 (in humans, mice have 12). They detect, gram+ (TLR2), gram - (TLR4), dsDNA, foreign RNA, etc.... So mRNA was leading to activation of TLR7, which basically made the body activate the innate immune system, you would feel like crap, the mRNA would get destroyed and you wouldn't develop protective immunity. So synthetic nucleotides were made that allowed escape from that TLR7 activation allowing a productive adaptive immune response to take place.

This is a table from the review that highlights hurdles that have been overcome to allow mRNA vaccines to be a possibility.

Box 1: Strategies for optimizing mRNA pharmacology​

A number of technologies are currently used to improve the pharmacological aspects of mRNA. The various mRNA modifications used and their impact are summarized below.
• Synthetic cap analogues and capping enzymes26,27 stabilize mRNA and increase protein translation via binding to eukaryotic translation initiation factor 4E (EIF4E)
• Regulatory elements in the 5′-untranslated region (UTR) and the 3′-UTR23 stabilize mRNA and increase protein translation
• Poly(A) tail25 stabilizes mRNA and increases protein translation
Modified nucleosides9,48 decrease innate immune activation and increase translation
• Separation and/or purification techniques: RNase III treatment (N.P. and D.W., unpublished observations) and fast protein liquid chromatography (FPLC) purification13 decrease immune activation and increase translation
• Sequence and/or codon optimization29 increase translation
• Modulation of target cells: co-delivery of translation initiation factors and other methods alters translation and immunogenicity
 
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Native

ToungeInCheek since 2010
Staff member
10 Year Member
I don’t really think the purpose of this thread is to spend time on the debates and not really fair as it is one sided! Locked thread.
Anyway… for the interested, I think these two articles take a fair approach to the lab leak theory and are good reading.


 

Native

ToungeInCheek since 2010
Staff member
10 Year Member
I know there is a great mask debate. This is pretty compelling that masks provide protection for other respiratory illnesses even when there is compliance, quality of masks, proper use etc etc.

 
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