If you put it into google translate, the abstract contains the following:

"In the biodistribution test, luciferase RNA-encapsulated LNP was intramuscularly administered to BALB / c mice. theAs a result, the expression of luciferase was observed at the administration site, and the expression level was lower than that in the liver.Was also recognized. Expression at the administration site of luciferase was observed from 6 hours after administration, and 9 days after administration.Disappeared. Expression in the liver was also observed 6 hours after administration and disappeared by 48 hours after administration. Also,Intramuscular administration of radiolabeled LNP encapsulating luciferase RNA to rats to quantify biodistributionUpon evaluation, the radioactivity concentration was the highest at the administration site. Liver is highest except at the administration siteIt was good (up to 18% of the dose)."

Another translation (via DeepL) of the first part of the same paragraph:

In the biodistribution study, luciferase RNA-encapsulated LNP was administered intramuscularly to BALB/c mice, and the expression of luciferase was observed at the site of administration, and also in the liver, although at a lower level. The expression of luciferase at the site of administration was observed from 6 hours post-dose and disappeared by 9 days post-dose. The luciferase was also observed in the liver at 6 hours post-dose and disappeared by 48 hours post-dose.

Does this mean that they tracked the actual distribution of the vaccine in the body of the rats, or was it just a study of the lipid byproducts?

  • $\begingroup$ Since they are using luciferase, which emits light I would guess direct observation. $\endgroup$
    – John
    Jul 26 '21 at 3:45
  • $\begingroup$ Would this study be a reliable measure of the distribution of the spike protein throughout the body? Or no? $\endgroup$ Jul 26 '21 at 4:13
  • $\begingroup$ Note the DeepL translation says expression was lower in liver while GoogTrans says the opposite. The length of expression, though, they agree was shorter in the liver. $\endgroup$
    – mgkrebbs
    Jul 26 '21 at 20:42

It looks like they're using the luciferase RNA as a substitute for the actual mRNA used in the vaccine because, since luciferase emits light when exposed to its substrate, it's easy to measure the expression and it's commonly used as a reporter for gene expression in many contexts. As far as I can tell, they seem to be using the same LNP formulation as the real vaccine, the only difference is the luciferase RNA substituted for the spike one. Unless there's a difference in how luciferase protein is expressed compared with spike (this seems unlikely to me), this experiment probably accurately reflects where spike is expressed after vaccination.

[disclaimer: I do not speak Japanese, and am answering with a great deal of assistance from Google Translate]

  • $\begingroup$ I have people telling me with absolute conviction that this study is only a study of where the lipid byproducts end up -- you're saying it is NOT that and is a genuine bio-distribution study of where the vaccine is delivered? $\endgroup$ Jul 26 '21 at 19:58
  • 1
    $\begingroup$ @sakurashinken As far as I can tell there is only luciferase RNA included, no luciferase protein. So, the only way they'd get luciferase activity would be if the thing they are injecting is getting RNA into cells that are then translating it into protein. So it's a measure of "if we deliver mRNA this way, where are the cells that end up translating that mRNA". It's a different mRNA than that which produces the viral spikes, but the presumption they make is that the delivery vehicle is what matters for distribution, not the identity of the transcript. $\endgroup$
    – Bryan Krause
    Jul 26 '21 at 20:41
  • $\begingroup$ Thank you for the clarification. $\endgroup$ Jul 26 '21 at 20:50

There are at least three types of studies being described. In a paragraph before the quoted one, they talk about testing for the PEGylated lipids ALC-0315 and ALC-0159 in plasma, liver, urine, and feces. The lipids rapidly moved from the blood to the liver, and were found in the feces; none were detected in the urine.

The other two kinds of studies are described in the quoted paragraph. One studied the protein product produced by the animal's cells from the administered mRNA coding for luciferase. The cell product is detected by the light it emits. The luciferase was detected both at the site of injection and in the liver, and continued being detected at the injection site for much longer.

The last study was of the same kind of mRNA nanoparticles, except that these were radioactively labeled. The radioactivity from them was detected at the injection site and in the liver. This indicates there were nanoparticles (or the radioactive components of them) present in both places.

So they tracked the lipids, and either the whole vaccine nanoparticles or some other component of them, but also, and most significantly, they tracked the animal's cellular product of the vaccine's mRNA (luciferase, standing in for the true vaccine's spike protein).

  • $\begingroup$ Thanks. When we see the data from Radiolabeled [Cholesteryl-1,2-3H(N)]-Cholesteryl Hexadecyl Ether, are we tracking just the nano-particles, and the luciferase is tracking where the spike protein would have expressed? Are the two correlated or not? This is a major sticking point as to what was being measured. $\endgroup$ Jul 26 '21 at 21:43
  • $\begingroup$ Since it's a lipid envelope component that was radiolabeled, that test tracks that part of the envelope, whether or not the nanoparticle remains intact. The luciferase measures a quite a different thing, a protein constructed by the animal following instructions of the mRNA. They would be correlated only in that both lipid and mRNA entered as parts of the nanoparticles. They go their separate ways. $\endgroup$
    – mgkrebbs
    Jul 26 '21 at 21:55

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