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Anthony J Leonardi Profile picture
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15 Nov, 4 tweets, 2 min read
@stanleyqilab I think your Crispr package would be well delivered by B cells. They traverse all organs and bone marrow and even play a part in neuroregeneration. Shedding vesicles all the while that can be loaded with RNA. @AnImmunologist @ExcisionBiotx pnas.org/content/117/9/…
sciencedirect.com/science/articl…
ncbi.nlm.nih.gov/pmc/articles/P…
ncbi.nlm.nih.gov/pmc/articles/P…

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More from @fitterhappierAJ

Anthony J Leonardi Profile picture
17 Nov
I'm going to briefly touch upon one of my favorite subjects: immunological memory. nytimes.com/2020/11/17/hea…
2/ First the B cells: I think for Covid-19 these are the most important to prevent infection and reinfection severity. In this large study on B cell memory, the authors see B cells turning into what we can presume is long-lived memory while continually (for the majorit of people)
3/ shedding Antibodies. Antibody shedding is great because it can control virus that rears its ugly head, and prevent virus from going into a new cell. So that's good. I am worried, though, that there may be cells with a reservoir of competent virus that is influencing this. We
Read 11 tweets
Anthony J Leonardi Profile picture
24 Sep
Back in May I said this paper suggested that orf8 was making it hard for the immune system to clear the virus due to the downregulation of MHC I, and that it forced it to age and compensate for this effect. Compensation can occur with ↑ interferon, the cytokine for inflammation
Recently there was a mutated virus in the wild that showed when the orf8 was nonfunctional, it only caused light illness. I believe that it's light illness bc the immune system no longer has to age and produce interferon so much in order to rec. and clear thelancet.com/journals/lance…
I elaborate on this a little more here
Read 8 tweets
Anthony J Leonardi Profile picture
19 Sep
After infection you lose A LOT of your naive T cells. Then, not having naive t cells predisposes you to baad outcomes the second go around. I've been saying it. cell.com/cell/fulltext/… Image
cell.com/cell/fulltext/…
Read 5 tweets
Anthony J Leonardi Profile picture
9 Sep
biorxiv.org/content/10.110…
1/Two things: Given the lack of t cell infiltrates, is this due to a lack of MHC expression on the surrounding cells? This stain should have been done as a mechanistic enquiry, I know canonically neurons do not express it but there is cross presentation by surrounding cells.
2/Perhaps it was and I read it wrong. Unknown; and wondering if the other viruses mentioned also have the leukopenic phenotype this does. The dying people aren't typical cases- there could be reasons they failed to have immune inflitrates, but the finding is significant and
Read 5 tweets
Anthony J Leonardi Profile picture
8 Sep
1/Analysis: this statement is not reassuring, but whenever you see 'someone familiar with the thinking,' you have license to be very skeptical. If I were to trust it, I would imagine other candidates would be less interested in GB and more interested in ADE. I'd like to reiterate Image
2/there is no 'herd immunity' with this virus via infection. You have heard it very early from me- the virus ages and deranges t cells through a similar mechanism to ebola and other lympho-manipulative pathogens. misc data published recently reiterated this, although it was not
3/the focus of the text- a shame, really. In a worst case scenario the vaccine would buy us time before sufficient escape, but then could become a liability. Even then, antibody cocktails can bridge us. In a worst case scenario we can have immune systems
Read 4 tweets
Anthony J Leonardi Profile picture
1 Sep
1/Friends, I have written up the thoughts I have on the immunopathology of COVID and how to prevent the exubeerant immune activation that causes pulmonary infiltration by lymphocytes. Especially pertinent were the papers of Israelow and Mathew that both osf.io/2egsm/
2/characterized the immune programs and suggested mechanism. I filed a patent application only to not get scooped- I have seen work taken from Nobel Prize winners so for someone less than Zizek's nothing it was important. I don't foresee patent award in the future.
Best drug is made by @Merck so I wish them godspeed if they choose to do this. AKT inhibitors are well characterized- there were trials @theNCI and certain immunotherapy companies like kite pharma and bluebird etc have used or explore their use.
Read 12 tweets

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