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wanderer_jasnah's profile
Jasnah Kholin - 8964 - ACAB - 💉💉
Jasnah Kholin - 8964 - ACAB - 💉💉
Jasnah Kholin - 8964 - ACAB -  💉 💉
@wanderer_jasnah

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Jasnah Kholin - 8964 - ACAB -  💉 💉

@wanderer_jasnah

HKer. RNA Virologist working on nidovirus/immune system interactions. Insomniac. Life before death. Journey before destination. 一个健康的社會不該只有一種聲音. 解散警隊. ★ she/佢 ★

大學,香港 || 仍然自由自我 永遠高唱我歌 走遍千里
Joined December 2016

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    Jasnah Kholin - 8964 - ACAB -  💉 💉‏ @wanderer_jasnah 16 Jun 2021

    Jasnah Kholin - 8964 - ACAB -  💉 💉 Retweeted Carl Zimmer

    my suspicion: most of this is CureVac using uridine instead of m1Ψ in the mRNA itsself... you're likely to accidentally hit RIG-I/MDA5 before the ribosome that way & wind up w/translational shutdown via phosphorylation of eIF2α after induction of ISGs...https://twitter.com/carlzimmer/status/1405265461579685890 …

    Jasnah Kholin - 8964 - ACAB -  💉 💉 added,

    Carl ZimmerVerified account @carlzimmer
    Ouch. CureVac reports an efficacy of just 47 percent against Covid-19 in a preliminary analysis of their Phase 3 trial. Here’s my @nytimes story https://www.nytimes.com/2021/06/16/health/curevac-vaccine.html …
    2:07 PM - 16 Jun 2021
    • 48 Retweets
    • 209 Likes
    • lailsb Buns for shoes x4 Liz Highleyman Dr. Angela Rasmussen Gunhild Alvik Nyborg Emma Touizer Josh Martine Mounier Sarah Zhang
    22 replies 48 retweets 209 likes
      1. Jasnah Kholin - 8964 - ACAB -  💉 💉‏ @wanderer_jasnah 16 Jun 2021

        okay so they're prolly actually hitting TLRs & not RIG-I-likes (i blame my bias there on being a coronavirologist lol) but otherwise the rest of my tweet still stands.

        1 reply 3 retweets 33 likes
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      2. Rufus Spivey Green‏ @RufusSG 16 Jun 2021
        Replying to @wanderer_jasnah

        Is there a simple explanation for noobs

        2 replies 0 retweets 11 likes
      3. Jasnah Kholin - 8964 - ACAB -  💉 💉‏ @wanderer_jasnah 16 Jun 2021
        Replying to @RufusSG

        so a big problem w/the early days of mRNA therapeutics is that cells have innate immune sensors designed to detect viral RNA & prevent it from getting out of hand, usually this occurs via shutting down translation temporarily or in the worst case activating RNase L...

        3 replies 3 retweets 56 likes
      4. Show replies
      1. Dr Brian Ferguson‏ @viropractor 16 Jun 2021
        Replying to @wanderer_jasnah

        Totally agree. quite possibly too much IFN and not enough spike expression

        0 replies 1 retweet 15 likes
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      2. Daniel Dimmock‏ @DanielDimmock2 16 Jun 2021
        Replying to @wanderer_jasnah

        IIRC curevac were also adding a protein backbone to their mRNAs to activate TLR7/8 for innate recruitment to try increase AB production ( agoniats being trialled as adjuvants) which mythed me as, like you said, Karikos work on modified nucleosides to avoid TLRs is v important.

        4 replies 1 retweet 15 likes
      3. Daniel Dimmock‏ @DanielDimmock2 16 Jun 2021
        Replying to @DanielDimmock2 @wanderer_jasnah

        I'll dig the papers out when I can!

        1 reply 0 retweets 2 likes
      4. End of conversation
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      2. Jasnah Kholin - 8964 - ACAB -  💉 💉‏ @wanderer_jasnah 16 Jun 2021
        Replying to @TonyBurnetti

        many things, for TLR7/8 it's the mRNA not ending up in endosomes, for RIG-I-like sensors it's structural features that we're still not fully done mapping. mRNA production & decay is very tightly controlled, a random bunch of exogeneous mRNA has many potential failure modes.

        1 reply 1 retweet 13 likes
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      2. Alex Merz‏ @Merz 16 Jun 2021
        Replying to @wanderer_jasnah

        Mentioned elsewhere in the thread, but the use of the beta-S-ARCA synthetic 5'-cap analog also seems to be incredibly important. Compare filled triangles to filled circles on the graph. https://pubmed.ncbi.nlm.nih.gov/20410931/ pic.twitter.com/YtEQFHgXUo

        4 replies 3 retweets 15 likes
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