{"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":"toxicidade-do-lnp-em-funcao-do-comprimento-da-cadeia-de-cavilhas","status":"publish","type":"post","link":"https:\/\/csiag.de\/pt\/blog\/2025\/06\/02\/toxizitaet-der-lnp-in-abhaengigkeit-der-laenge-der-peg-kette\/","title":{"rendered":"Toxicidade dos LNP em fun\u00e7\u00e3o do comprimento da cadeia PEG"},"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\">\u00cdndice<\/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\/pt\/blog\/2025\/06\/02\/toxizitaet-der-lnp-in-abhaengigkeit-der-laenge-der-peg-kette\/#Welche_LNPs_wurden_verwendet\" >Que LNP foram utilizados?<\/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\/pt\/blog\/2025\/06\/02\/toxizitaet-der-lnp-in-abhaengigkeit-der-laenge-der-peg-kette\/#Toxizitat_wurde_nicht_durch_Studien_uberpruft\" >A toxicidade n\u00e3o foi comprovada por estudos<\/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\/pt\/blog\/2025\/06\/02\/toxizitaet-der-lnp-in-abhaengigkeit-der-laenge-der-peg-kette\/#Akkumulation_in_der_Leber\" >Acumula\u00e7\u00e3o no f\u00edgado<\/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\/pt\/blog\/2025\/06\/02\/toxizitaet-der-lnp-in-abhaengigkeit-der-laenge-der-peg-kette\/#Der_Weg_in_die_Leber_und_die_Lange_der_Kette\" >O caminho para o f\u00edgado e o comprimento da cadeia<\/a><\/li><\/ul><\/nav><\/div>\n\n<p class=\"wp-block-paragraph\">Quanto mais curta for a cadeia de PEG (polietilenoglicol), maior ser\u00e1 a toxicidade da LNP. A BioNTech explica este facto na sua <a href=\"https:\/\/www.mdpi.com\/2227-9059\/9\/5\/530\" target=\"_blank\" rel=\"noreferrer noopener\">Publica\u00e7\u00e3o<\/a> \"Non-Immunotherapy Application of LNP-mRNA: Maximising Efficacy and Safety\" de 10.05.2021, embora com uma reda\u00e7\u00e3o - ligeiramente - diferente: \"Maximising Efficacy\".<br>A toxicidade baseia-se no facto de os tr\u00eas l\u00edpidos cati\u00f3nicos ioniz\u00e1veis n\u00e3o serem biodegrad\u00e1veis e de a sua inevit\u00e1vel acumula\u00e7\u00e3o no organismo ter consequ\u00eancias citot\u00f3xicas.<\/p>\n\n\n\n<h2 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Welche_LNPs_wurden_verwendet\"><\/span>Que LNP foram utilizados?<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> (ioniz\u00e1veis) e <a href=\"https:\/\/www.echelon-inc.com\/product\/alc-0159\/\" target=\"_blank\" rel=\"noreferrer noopener\">ALC-0159<\/a> (PEGilado)<br><em>Moderna<\/em> - <a href=\"https:\/\/www.echelon-inc.com\/product\/sm-102\/\" target=\"_blank\" rel=\"noreferrer noopener\">SM-102<\/a> (ioniz\u00e1veis) e <a href=\"https:\/\/www.echelon-inc.com\/product\/dmg-peg-2000\/\" target=\"_blank\" rel=\"noreferrer noopener\">PEG2000-DMG<\/a> (PEGilado)<\/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\">Para todos os l\u00edpidos acima mencionados, os fabricantes (por exemplo <a href=\"https:\/\/www.echelon-inc.com\/product\/alc-0315\/#tab-description\" target=\"_blank\" rel=\"noreferrer noopener\">Echelon Biosciences<\/a>) \"... Este \u00e9 um produto de grau reagente, apenas para uso em investiga\u00e7\u00e3o.\"<\/p>\n\n\n\n<h2 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Toxizitat_wurde_nicht_durch_Studien_uberpruft\"><\/span>A toxicidade n\u00e3o foi comprovada por estudos<span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<p class=\"wp-block-paragraph\">De acordo com o <a href=\"https:\/\/www.tga.gov.au\/sites\/default\/files\/foi-2389-06.pdf\" target=\"_blank\" rel=\"noreferrer noopener\">Publica\u00e7\u00e3o<\/a> \"Relat\u00f3rio de avalia\u00e7\u00e3o n\u00e3o cl\u00ednica BNT 162b2 mRNA COVID-19 vacina COMIRNATY\u2122\" do Governo australiano - Departamento de Sa\u00fade de janeiro de 2021 pode ser lido na p\u00e1gina 11: \"A toxicidade da formula\u00e7\u00e3o LNP ou dos novos excipientes isoladamente n\u00e3o foi especificamente estudada.\"<br>Por outras palavras, n\u00e3o foram realizados estudos de toxicidade sobre a utiliza\u00e7\u00e3o e os efeitos dos novos excipientes de LNP acima mencionados.<\/p>\n\n\n\n<h2 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Akkumulation_in_der_Leber\"><\/span>Acumula\u00e7\u00e3o no f\u00edgado<span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<p class=\"wp-block-paragraph\">Muitos medicamentos s\u00e3o parcial ou totalmente metabolizados pelo f\u00edgado e entram na corrente sangu\u00ednea. O excipiente ALC-315 acima mencionado tamb\u00e9m se acumula no f\u00edgado, como se pode ver no <a href=\"https:\/\/www.judicialwatch.org\/wp-content\/uploads\/2022\/03\/JW-v-HHS-prod-3-02418.pdf\" target=\"_blank\" rel=\"noreferrer noopener\">Resposta parcial \u00e0 pergunta n.\u00ba 2021-4379<\/a> ao abrigo da Lei da Liberdade de Informa\u00e7\u00e3o (FOIA), que \u00e9 objeto da queixa no processo Judicial Watch, Inc. v. U.S. Department of Health and Human Services (21-cv-2418), atualmente pendente no Tribunal Distrital dos EUA para o Distrito de Columbia, na p\u00e1gina 16 de 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\">Tamb\u00e9m mencionado na p\u00e1gina 45 do relat\u00f3rio acima referido. <a href=\"https:\/\/www.tga.gov.au\/sites\/default\/files\/foi-2389-06.pdf\" target=\"_blank\" rel=\"noopener\">Relat\u00f3rios<\/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\">Na p\u00e1gina 46, a via metab\u00f3lica puramente te\u00f3rica \u00e9 descrita com base em experi\u00eancias in vitro, embora n\u00e3o tenha sido verificada no ser humano.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Enquanto <a href=\"https:\/\/www.statnews.com\/2017\/01\/10\/moderna-trouble-mrna\/\" target=\"_blank\" rel=\"noreferrer noopener\">Moderna<\/a> interrompeu o ALC-0315 devido a incompatibilidade hep\u00e1tica e desenvolveu ela pr\u00f3pria a plataforma SM (o ALC-0315 tinha-se revelado demasiado t\u00f3xico para a terapia gen\u00e9tica da doen\u00e7a hep\u00e1tica s\u00edndrome de Crigler-Najjar, pelo que o ent\u00e3o parceiro de investiga\u00e7\u00e3o <em>Alexion<\/em> interrompeu o estudo por raz\u00f5es de seguran\u00e7a), a BioNTech \/ Pfizer continua a utiliz\u00e1-los contra a sua vontade.<\/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>O caminho para o f\u00edgado e o comprimento da cadeia<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\">... ser\u00e1 continuado ...<\/p>","protected":false},"excerpt":{"rendered":"<p>Quanto mais curta for a cadeia de PEG (polietilenoglicol), maior ser\u00e1 a toxicidade do LNP. A BioNTech explica este facto na sua publica\u00e7\u00e3o \"Non-Immunotherapy Application of LNP-mRNA: Maximising Efficacy and Safety\" de 10.05.2021, embora com uma reda\u00e7\u00e3o - um pouco - diferente: \"Maximising Efficacy\". A toxicidade baseia-se no facto de os tr\u00eas l\u00edpidos cati\u00f3nicos ioniz\u00e1veis n\u00e3o serem biodegrad\u00e1veis e de a sua toxicidade ser, portanto,...&nbsp;<a href=\"https:\/\/csiag.de\/pt\/blog\/2025\/06\/02\/toxizitaet-der-lnp-in-abhaengigkeit-der-laenge-der-peg-kette\/\" rel=\"bookmark\">Ler mais \"<span class=\"screen-reader-text\">Toxicidade dos LNP em fun\u00e7\u00e3o do comprimento da cadeia PEG<\/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\/pt\/wp-json\/wp\/v2\/posts\/10036","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/csiag.de\/pt\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/csiag.de\/pt\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/csiag.de\/pt\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/csiag.de\/pt\/wp-json\/wp\/v2\/comments?post=10036"}],"version-history":[{"count":0,"href":"https:\/\/csiag.de\/pt\/wp-json\/wp\/v2\/posts\/10036\/revisions"}],"wp:attachment":[{"href":"https:\/\/csiag.de\/pt\/wp-json\/wp\/v2\/media?parent=10036"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/csiag.de\/pt\/wp-json\/wp\/v2\/categories?post=10036"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/csiag.de\/pt\/wp-json\/wp\/v2\/tags?post=10036"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}