After hours at the DMV, at closing, a DMV employee comes out and says “All hope is lost, there is no point, everyone should go home.” I said that’s the most earnest, honest depressing thing I’ve heard all day.
“Well, it could be worse. You could have my job,” she says.
“Sorry, we are at full capacity.” (4:30 PM)
This is the sixth time I’ve tried to go to the DMV to renew my license.
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1/4 SARS-CoV-2 Orf6 appears to hijack nuclear import machinery, inhibiting nuclear translocation of key signaling and cell proliferation molecules such as STAT1 and STAT2. This is another way that SARS-CoV-2 downregulates intracellular immune responses such (e.g. interferon --).
2/4 These findings also meld with prior data demonstrating nuclear translocation of SARS-CoV-2. Coupled, these data suggest that the virus has evolved multiple mechanisms for avoiding both extracellular adaptive immune responses, as well as intracellular immunity / host defenses.
3/4 These findings could also lead to future discoveries about the genesis and pathogenesis of "long COVID" and repeat infections, coupled to the discovery of SARS-CoV-2 building up deep in tissues that are not as accessible to the immune system.
We took this image of CRISPR-Cas9 (green) being delivered to a T cell using our targeting peptide tech, which was the first demonstration of CRISPR delivery to a primary human T cell with a non-viral nanocarrier as of 2018, AFAIK. We achieved 34% editing.
Green: CRISPR-Cas9 ribonucleoprotein delivered via peptide nanocarriers
Blue: nucleus
Red: cytosol
Scale bar: 500 nanometers
Imaging: super-resolution microscopy
Using this sort of tech, you can target and manipulate specific cell types with arbitrary genetic code, both in permanent (e.g. CRISPR-Cas9) and temporary (e.g. mRNA) ways. T cell editing is particularly relevant in the fields of immuno-oncology and autoimmune diseases.
My ACE2 cloak hypothesis is shifting a bit. Soluble and membrane-bound ACE2 is clearly not fully saturating all exposed neutralizing antibody sites, and some B cells are binding. Still, ACE2 cloaking suggests that small numbers of virus get fully cloaked.
Alternatively to the ACE2 cloaking, the virus still has some shielding mechanisms alternative to that including glycosylation and going from closed to open conformations. In “open” state, ACE2 would bias the thermodynamics of B cell binding to the spike protein...
...and the subsequent antibody-generating response, to be preferential to other sites. Doesn’t mean that B cells won’t stick to neutralizing site at all.
This is in a large part driven by ACE2 existing both as a soluble and membrane-bound protein.
Why has @BARDA / @HHSGov suspended its funding for immunomodulators and therapeutics that "improve the clinical response and/or resolution of symptoms associated with... viral respiratory infections" as well as for "pre- and post-exposure prophylaxis" approaches?
When considering the flaws in spike protein vaccine development, and that @BARDA has shelled out >$2Bn to just five companies developing spike protein vaccines, it almost seems like no one wants to fund preventative or effective therapeutic approaches to this virus. Why is that?
"[T]herapeutics... or the use of post-event prophylaxis will be the preferred strategy... Priority will be placed on [medical countermeasures] that focus on post-event prophylaxis or post-exposure treatment."
I recommend reading about immunological synapses to better understand how various immune cells (particularly T cells and NK cells) can grab onto antigens and aid B cells in maturing higher affinity BCRs and antibodies, as well as encourage division
I bought a one-way ticket to Silicon Valley when I was 21. I had just finished my bachelor’s in Biomedical Engineering at Rensselaer Polytechnic Institute where I worked with TALENs and created a gene editing, nanoparticle-based delivery system for editing mice.
The first years were tough. People would always ask, “what makes you think you can...” style questions. VCs would play games. It was like Silicon Valley, the TV show.
In 2017 we raised a seed round. With that cash we built a state-of-the-art, highly automated lab capable of everything from peptide synthesis to fluid handling automation and automated cell imaging, with integrated data outputs.