{"id":10036,"date":"2025-06-02T19:05:44","date_gmt":"2025-06-02T19:05:44","guid":{"rendered":"https:\/\/csiag.de\/?p=10036"},"modified":"2025-06-03T20:37:17","modified_gmt":"2025-06-03T20:37:17","slug":"toxicity-of-the-lnp-depending-on-the-length-of-the-peg-chain","status":"publish","type":"post","link":"https:\/\/csiag.de\/en\/blog\/2025\/06\/02\/toxizitaet-der-lnp-in-abhaengigkeit-der-laenge-der-peg-kette\/","title":{"rendered":"Toxicity of LNP depending on the length of the PEG chain"},"content":{"rendered":"<div id=\"ez-toc-container\" class=\"ez-toc-v2_0_85 counter-hierarchy ez-toc-counter ez-toc-grey ez-toc-container-direction\">\n<div class=\"ez-toc-title-container\">\n<p class=\"ez-toc-title\" style=\"cursor:inherit\">Table of contents<\/p>\n<span class=\"ez-toc-title-toggle\"><\/span><\/div>\n<nav><ul class='ez-toc-list ez-toc-list-level-1' ><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-1\" href=\"https:\/\/csiag.de\/en\/blog\/2025\/06\/02\/toxizitaet-der-lnp-in-abhaengigkeit-der-laenge-der-peg-kette\/#Welche_LNPs_wurden_verwendet\" >Which LNPs were used?<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-2\" href=\"https:\/\/csiag.de\/en\/blog\/2025\/06\/02\/toxizitaet-der-lnp-in-abhaengigkeit-der-laenge-der-peg-kette\/#Toxizitat_wurde_nicht_durch_Studien_uberpruft\" >Toxicity has not been verified by studies<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-3\" href=\"https:\/\/csiag.de\/en\/blog\/2025\/06\/02\/toxizitaet-der-lnp-in-abhaengigkeit-der-laenge-der-peg-kette\/#Akkumulation_in_der_Leber\" >Accumulation in the liver<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-4\" href=\"https:\/\/csiag.de\/en\/blog\/2025\/06\/02\/toxizitaet-der-lnp-in-abhaengigkeit-der-laenge-der-peg-kette\/#Der_Weg_in_die_Leber_und_die_Lange_der_Kette\" >The path into the liver and the length of the chain<\/a><\/li><\/ul><\/nav><\/div>\n<span class=\"span-reading-time rt-reading-time\" style=\"display: block;\"><span class=\"rt-label rt-prefix\">Reading time<\/span> <span class=\"rt-time\"> 2<\/span> <span class=\"rt-label rt-postfix\">minutes<\/span><\/span>\n<p class=\"wp-block-paragraph\">The shorter the PEG chain (polyethylene glycol), the higher the toxicity of the LNP. BioNTech explains this in its <a href=\"https:\/\/www.mdpi.com\/2227-9059\/9\/5\/530\" target=\"_blank\" rel=\"noreferrer noopener\">publication<\/a> \"Non-Immunotherapy Application of LNP-mRNA: Maximizing Efficacy and Safety\" of 10.05.2021, albeit formulated - somewhat - differently: \"Maximizing Efficacy\".<br>The toxicity is based on the fact that all three of the ionizable cationic lipids are not biodegradable and their inevitable accumulation in the body has cytotoxic consequences.<\/p>\n\n\n\n<h2 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Welche_LNPs_wurden_verwendet\"><\/span>Which LNPs were used?<span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<p class=\"wp-block-paragraph\"><em>Pfizer<\/em> \/ <em>BioNTech<\/em> - BNT162b2 - <a href=\"https:\/\/www.echelon-inc.com\/product\/alc-0315\/\" target=\"_blank\" rel=\"noreferrer noopener\">ALC-0315<\/a> (ionizable) and <a href=\"https:\/\/www.echelon-inc.com\/product\/alc-0159\/\" target=\"_blank\" rel=\"noreferrer noopener\">ALC-0159<\/a> (PEGylated)<br><em>Moderna<\/em> - <a href=\"https:\/\/www.echelon-inc.com\/product\/sm-102\/\" target=\"_blank\" rel=\"noreferrer noopener\">SM-102<\/a> (ionizable) and <a href=\"https:\/\/www.echelon-inc.com\/product\/dmg-peg-2000\/\" target=\"_blank\" rel=\"noreferrer noopener\">PEG2000-DMG<\/a> (PEGylated)<\/p>\n\n\n<div class=\"wp-block-image\">\n<figure class=\"aligncenter size-large\"><img decoding=\"async\" width=\"1024\" height=\"562\" src=\"https:\/\/csiag.de\/wp-content\/uploads\/2025\/06\/image-1024x562.png\" alt=\"\" class=\"wp-image-10045\" srcset=\"https:\/\/csiag.de\/wp-content\/uploads\/2025\/06\/image-1024x562.png 1024w, https:\/\/csiag.de\/wp-content\/uploads\/2025\/06\/image-300x165.png 300w, https:\/\/csiag.de\/wp-content\/uploads\/2025\/06\/image-768x421.png 768w, https:\/\/csiag.de\/wp-content\/uploads\/2025\/06\/image-18x10.png 18w, https:\/\/csiag.de\/wp-content\/uploads\/2025\/06\/image.png 1456w\" sizes=\"(max-width: 1024px) 100vw, 1024px\" \/><\/figure>\n<\/div>\n\n\n<p class=\"wp-block-paragraph\">For all the lipids mentioned above, the manufacturers (e.g. <a href=\"https:\/\/www.echelon-inc.com\/product\/alc-0315\/#tab-description\" target=\"_blank\" rel=\"noreferrer noopener\">Echelon Biosciences<\/a>) \"... This is a reagent grade product, for research use only.\"<\/p>\n\n\n\n<h2 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Toxizitat_wurde_nicht_durch_Studien_uberpruft\"><\/span>Toxicity has not been verified by studies<span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<p class=\"wp-block-paragraph\">According to the <a href=\"https:\/\/www.tga.gov.au\/sites\/default\/files\/foi-2389-06.pdf\" target=\"_blank\" rel=\"noreferrer noopener\">Publication<\/a> \"Nonclinical Evaluation Report BNT 162b2 mRNA COVID-19 vaccine COMIRNATY\u2122\" of the Australian Government - Department of Health from January 2021 can be read on page 11: \"The toxicity of LNP formulation or the novel excipients alone was not specifically studied.\"<br>In other words, no toxicity studies have been conducted on the use and effects of the new LNP excipients mentioned above.<\/p>\n\n\n\n<h2 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Akkumulation_in_der_Leber\"><\/span>Accumulation in the liver<span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<p class=\"wp-block-paragraph\">Many drugs are partially or completely metabolized by the liver and enter the bloodstream. The above-mentioned excipient ALC-315 also accumulates in the liver, as can be seen from the <a href=\"https:\/\/www.judicialwatch.org\/wp-content\/uploads\/2022\/03\/JW-v-HHS-prod-3-02418.pdf\" target=\"_blank\" rel=\"noreferrer noopener\">Partial answer to question no. 2021-4379<\/a> under the Freedom of Information Act (FOIA), which is the subject of the complaint in Judicial Watch, Inc. v. U.S. Department of Health and Human Services (21-cv-2418), currently pending in the U.S. District Court for the District of Columbia, at page 16 of 466:<\/p>\n\n\n\n<figure class=\"wp-block-image size-large\"><img decoding=\"async\" width=\"1024\" height=\"542\" src=\"https:\/\/csiag.de\/wp-content\/uploads\/2025\/06\/image-3-1024x542.png\" alt=\"\" class=\"wp-image-10054\" srcset=\"https:\/\/csiag.de\/wp-content\/uploads\/2025\/06\/image-3-1024x542.png 1024w, https:\/\/csiag.de\/wp-content\/uploads\/2025\/06\/image-3-300x159.png 300w, https:\/\/csiag.de\/wp-content\/uploads\/2025\/06\/image-3-768x407.png 768w, https:\/\/csiag.de\/wp-content\/uploads\/2025\/06\/image-3-18x10.png 18w, https:\/\/csiag.de\/wp-content\/uploads\/2025\/06\/image-3.png 1212w\" sizes=\"(max-width: 1024px) 100vw, 1024px\" \/><\/figure>\n\n\n\n<p class=\"wp-block-paragraph\">Also mentioned on page 45 of the above. <a href=\"https:\/\/www.tga.gov.au\/sites\/default\/files\/foi-2389-06.pdf\" target=\"_blank\" rel=\"noopener\">Reports<\/a>:<\/p>\n\n\n\n<figure class=\"wp-block-image size-large\"><img decoding=\"async\" width=\"1024\" height=\"55\" src=\"https:\/\/csiag.de\/wp-content\/uploads\/2025\/06\/image-4-1024x55.png\" alt=\"\" class=\"wp-image-10060\" srcset=\"https:\/\/csiag.de\/wp-content\/uploads\/2025\/06\/image-4-1024x55.png 1024w, https:\/\/csiag.de\/wp-content\/uploads\/2025\/06\/image-4-300x16.png 300w, https:\/\/csiag.de\/wp-content\/uploads\/2025\/06\/image-4-768x42.png 768w, https:\/\/csiag.de\/wp-content\/uploads\/2025\/06\/image-4-18x1.png 18w, https:\/\/csiag.de\/wp-content\/uploads\/2025\/06\/image-4.png 1218w\" sizes=\"(max-width: 1024px) 100vw, 1024px\" \/><\/figure>\n\n\n\n<p class=\"wp-block-paragraph\">On page 46, the purely theoretically assumed metabolic pathway is outlined on the basis of in vitro experiments, although this has not been verified in humans.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">While <a href=\"https:\/\/www.statnews.com\/2017\/01\/10\/moderna-trouble-mrna\/\" target=\"_blank\" rel=\"noreferrer noopener\">Moderna<\/a> parted company with ALC-0315 due to liver incompatibility and developed the SM platform itself (ALC-0315 had proven to be too toxic for gene therapy of the liver disease Crigler-Najjar syndrome, so that the then research partner <em>Alexion<\/em> stopped the study for safety reasons), BioNTech \/ Pfizer continues to use them against its better judgment.<\/p>\n\n\n\n<h2 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Der_Weg_in_die_Leber_und_die_Lange_der_Kette\"><\/span>The path into the liver and the length of the chain<span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<p class=\"wp-block-paragraph\"><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">\u2026 to be continued \u2026<\/p>","protected":false},"excerpt":{"rendered":"<p><span class=\"span-reading-time rt-reading-time\" style=\"display: block;\"><span class=\"rt-label rt-prefix\">Reading time<\/span> <span class=\"rt-time\"> 2<\/span> <span class=\"rt-label rt-postfix\">minutes<\/span><\/span>The shorter the PEG chain (polyethylene glycol), the higher the toxicity of the LNP. BioNTech explains this in its publication \"Non-Immunotherapy Application of LNP-mRNA: Maximizing Efficacy and Safety\" from 10.05.2021, albeit formulated - somewhat - differently: \"Maximizing Efficacy\".The toxicity is based on the fact that all three of the ionizable cationic lipids are non-biodegradable and their, thus...&nbsp;<a href=\"https:\/\/csiag.de\/en\/blog\/2025\/06\/02\/toxizitaet-der-lnp-in-abhaengigkeit-der-laenge-der-peg-kette\/\" rel=\"bookmark\">Read More \"<span class=\"screen-reader-text\">Toxicity of LNP depending on the length of the PEG chain<\/span><\/a><\/p>","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"_lmt_disableupdate":"","_lmt_disable":"","neve_meta_sidebar":"","neve_meta_container":"","neve_meta_enable_content_width":"","neve_meta_content_width":0,"neve_meta_title_alignment":"","neve_meta_author_avatar":"","neve_post_elements_order":"","neve_meta_disable_header":"","neve_meta_disable_footer":"","neve_meta_disable_title":"","footnotes":""},"categories":[628,316,1078],"tags":[5067,5066,5074,22,36,5080,5079,5069,5075,5071,4812,105,5073,5077,5070,5072,23,5076,5078,44],"class_list":["post-10036","post","type-post","status-publish","format-standard","hentry","category-corona","category-corona-blog","category-medizin","tag-alc-159","tag-alc-315","tag-alnylam","tag-biontech","tag-bnt162b2","tag-cholesterol","tag-dlin-mc3-dma","tag-dmg-peg2000","tag-elasomeran","tag-ionisierbar","tag-lnp","tag-moderna","tag-patisiran","tag-peg-lipid","tag-peg2000-dmg","tag-pegyliert","tag-pfizer","tag-phosholipid","tag-sterol","tag-tozinameran"],"acf":[],"modified_by":"Achim Goerner","_links":{"self":[{"href":"https:\/\/csiag.de\/en\/wp-json\/wp\/v2\/posts\/10036","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/csiag.de\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/csiag.de\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/csiag.de\/en\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/csiag.de\/en\/wp-json\/wp\/v2\/comments?post=10036"}],"version-history":[{"count":0,"href":"https:\/\/csiag.de\/en\/wp-json\/wp\/v2\/posts\/10036\/revisions"}],"wp:attachment":[{"href":"https:\/\/csiag.de\/en\/wp-json\/wp\/v2\/media?parent=10036"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/csiag.de\/en\/wp-json\/wp\/v2\/categories?post=10036"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/csiag.de\/en\/wp-json\/wp\/v2\/tags?post=10036"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}