Talk:ALC-0315

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Lipid?[edit]

I'm not sufficiently knowledgeable in organic chemistry to decide whether this is a lipid or not. I do know that it is described as a lipid (repeatedly) in the MHRA source (Medicines and Healthcare products Regulatory Agency (11 December 2020). "Public Assessment Report: Authorisation for Temporary Supply COVID-19 mRNA Vaccine BNT162b2" (PDF).). It is introduced thus therein:

In addition to those excipients, the vaccine contains four lipids, of which two are used in approved medicinal products (cholesterol and 1,2-distearoyl-sn-glycero-3-phosphocholine, hereafter termed DSPC) and two are considered novel in that they have not been used in an authorised medicinal product in the UK:

ALC-0315 ((4-hydroxybutyl)azanediyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate)) and ALC-0159 (2-[(polyethylene glycol)-2000]-N,N-ditetradecylacetamide).

Both ALC-0315 and ALC-0159 are repeatedly characterised as lipids. As for esters and amines, I find only this characterisation:

ALC-0315 and ALC-0159 are metabolised by hydrolytic metabolism of the ester and amide functionalities, respectively, and this hydrolytic metabolism is observed across the species evaluated.

@Graeme Bartlett: You categorised this article in Category:Esters and Category:Amines only. Neither is a subcategory of Category:Lipids. I suppose that at least some subcategory of the esters could be made a subcategory of lipids, too; from a quick browse of the article Ester I suspect that Category:Glycerol esters would be a candidate for such a double categorisation. Pending this, and placing these two ALC's in some such category, I put them directly into Category:Lipids, without removing any existing categorisation.

As I wrote, I'm extremely unsure about the factual correctness of this; I just lean on my interpretation of the MHRA ('reliable') source. If I'm wrong, then just revert. JoergenB (talk) 21:50, 30 January 2021 (UTC)[reply]

The definition of a lipid has more to do with its function than with its specific chemical composition. ALC-0315 has two 16-carbon carboxylic acids that are each esterified to another 6-carbon chain leading to a nitrogen atom. That combination means the compound as a whole will have very low water solubility and will mainly be located in the membrane portion of a cell rather than its aqueous part, although the amine will be protonated at physiological pH, which together with the butyl alcohol (the third attachment to the nitrogen) will give this "head" part some affinity for water, as in conventional surfactants. ALC-0315 was designed to be combined with ALC-0159 to form lipid nanoparticles capable of carrying the active ingredient of the vaccine into cells. I think that its quite correct to categorise ALC-0315 as a lipid independently of its categorisation as an ester and amine (and it is also a primary alcohol, although that's only a small portion of the overall structure). Mike Turnbull (talk) 14:29, 31 January 2021 (UTC)[reply]

Transfection target[edit]

In my opinion, anything about muscle cells (specifically) in relation to transfection should be removed from the page. The actual target for transfection are antigen-presenting cells, as described here: ^[1], but other cell types could be transfected as well: ^[2].

Done I've altered the wording of the sentence and included the Nature reference, which is a good review article. Mike Turnbull (talk) 18:07, 4 November 2021 (UTC)[reply]

References

authorisation[edit]

My understanding is that whilst this substance has been approved for research purposes in medicine and pharmaceutics, that there is actually no authorisation of this substance on use in humans (and the same for ALC-0159 - the other aspect of nanotechnology introduced in the Pfizer Vaccine). I've not been able to source any studies, abstracts, peer-reviewed publications or scholarly articles on its use in humans, its side-effects, and understand it can be toxic. As far as my understanding goes, the FDA approved its use within the vaccine without the correct PK studies (or any on these particular substances), nor was any toxicity/carcinogenicity testing done, and without these substances otherwise being tested for safety in humans. This is, of course, very concerning when it's been a very opaque process from start to finish, and with pfizer wishing to withhold data, unethically and unnecessarily (provided there's nothing to hide, of course). Perhaps you can investigate and get something noted about it here. My understanding of these substances is that theu shouldn't be being administered into human bodies... the fact they are, when last year at the annual World Economic Forum meeting (2020), a speech was done on how we need to " accept that we are no longer mysterious souls, but instead, "hackable animals ". Grossly concerning... with it being announced that Dr Fauci and Dr Baric misrepresented information entirely to the public, gain of function WAS funded and carried out when they said it wasn't, and the push for these vaccines to be taken without the correct testing and data... it's all too much. Wikipedia is massively used by many. Please look into this with me and help people like me to act on it... what is happening in the world is not ok. 2A02:C7F:3B81:A200:3D84:7E79:59FF:50FA (talk) 14:03, 23 December 2021 (UTC)[reply]

In the article, reference 5 is the MHRA document that shows the authorisation in the UK. Mike Turnbull (talk) 14:38, 23 December 2021 (UTC)[reply]

Its authorized literally everywhere the vaccine is authorized (which is to say "everywhere in the world"), because the vaccine is authorized an therefor its ingredients are. Wikipedia is not for this sort of speculative worry-wort stuff. Save the wierd original research for shouty youtube videos. Thats not what we do here. Duckmonster (talk) 15:16, 9 July 2022 (UTC)[reply]

Safety of ALC-0315 and ALC-0159[edit]

The investigative collective Correctiv asked the European Medicines Agency (EMA) on the safety of ALC-0315 and ALC-0159 and quoted the answer from the EMA:

"By entering the blood stream, lipid nanoparticles can come into contact (fuse) with many types of cells in the body and distribute the mRNA to different tissues. Animal models have been used to study how the components of the vaccine distribute to tissues other than the muscle into which they are injected.

These studies used much higher doses of vaccine to investigate its safety and found that the components, the mRNA and lipid nanoparticles, remain mainly at the injection site, with only small amounts able to reach other tissues, such as the liver. These studies give confidence that when vaccines are given to humans, no safety problems due to accumulation of lipid nanoparticles and mRNA in other tissues are expected."[1] (access-date: 2022-01-23) --Myosci (talk) 11:22, 23 January 2022 (UTC)[reply]

[1] ttps://www.nature.com/articles/s41573-021-00283-5.pdf

[2] ttps://www.sciencedirect.com/science/article/abs/pii/S1879625721000304?via%3Dihub

[1]

[2]