{"id":309,"date":"2021-09-18T08:38:21","date_gmt":"2021-09-18T00:38:21","guid":{"rendered":"http:\/\/phosphoramidite.cn\/en\/?p=309"},"modified":"2021-09-18T08:38:21","modified_gmt":"2021-09-18T00:38:21","slug":"lipid-nanoparticles-for-therapeutic-delivery-of-gti-2040","status":"publish","type":"post","link":"https:\/\/nugene.com.cn\/en\/index.php\/lipid-nanoparticles-for-therapeutic-delivery-of-gti-2040\/","title":{"rendered":"Lipid Nanoparticles for Therapeutic Delivery of GTI-2040"},"content":{"rendered":"\n<p>Mol Pharm<\/p>\n\n\n\n<ul class=\"wp-block-list\"><li><a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=%22Mol+Pharm%22%5Bjour%5D\"><\/a><\/li><li><a href=\"https:\/\/www.ncbi.nlm.nih.gov\/nlmcatalog?term=%22Mol+Pharm%22%5BTitle+Abbreviation%5D\"><\/a><\/li><li><a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/25871632\/#\"><\/a><\/li><\/ul>\n\n\n\n<p>.&nbsp;2015 Jun 1;12(6):2010-8.&nbsp;doi: 10.1021\/mp5008212.&nbsp;Epub 2015 Apr 28.<\/p>\n\n\n\n<p>D33-targeted lipid nanoparticles (aCD33LNs) were synthesized for delivery of GTI-2040, an antisense oligonucleotide (ASO) against the R2 subunit of ribonucleotide reductase, to acute myelogenous leukemia (AML). These LNs incorporated a deoxycholate-polyethylenimine (DOC-PEI) conjugate, which has shown significant activity to facilitate oligonucleotide delivery. Anti-CD33 scFv (aCD33) was added as a targeting ligand. The delivery efficiency of this system was investigated both in vitro and in vivo. When cells were treated with aCD33LN\/GTI-2040, significant uptake was observed in CD33 positive Kasumi-1 cells. aCD33LNs loaded with GTI-2040 induced significant down-regulation of R2 mRNA and protein levels in AML cells. Moreover, aCD33LN\/GTI-2040 showed a 15-fold reduction in the IC50 of antileukemic drug Ara-C in Kasumi-1 cells. In Kasumi-1 xenograft model, aCD33LN\/GTI-2040 showed significant R2 downregulation compared to LN\/GTI-2040. Furthermore, aCD33LN\/GTI-2040 coadministered with Ara-C was shown to be highly effective in tumor growth inhibition and to greatly increase survival time of mice bearing Kasumi-1 xenograft tumors. The conjugate DOC-PEI has shown an ability to include calcein release from lipid nanoparticles, suggesting a potential mechanism contributing to efficient endosome release by DOC-PEI2K. These results indicate that aCD33LNs are a highly effective vehicle for the therapeutic delivery of antisense agents to AML.<\/p>\n\n\n<p class=\"wp-block-tag-cloud\"><a href=\"https:\/\/nugene.com.cn\/en\/index.php\/tag\/3-deoxyadenosine\/\" class=\"tag-cloud-link tag-link-23 tag-link-position-1\" style=\"font-size: 8pt;\" aria-label=\"3\u2019-deoxyadenosine (1 item)\">3\u2019-deoxyadenosine<\/a>\n<a href=\"https:\/\/nugene.com.cn\/en\/index.php\/tag\/abogen\/\" class=\"tag-cloud-link tag-link-33 tag-link-position-2\" style=\"font-size: 8pt;\" aria-label=\"Abogen (1 item)\">Abogen<\/a>\n<a href=\"https:\/\/nugene.com.cn\/en\/index.php\/tag\/cansino-biologics\/\" class=\"tag-cloud-link tag-link-29 tag-link-position-3\" style=\"font-size: 8pt;\" aria-label=\"Cansino biologics (1 item)\">Cansino biologics<\/a>\n<a href=\"https:\/\/nugene.com.cn\/en\/index.php\/tag\/conference\/\" class=\"tag-cloud-link tag-link-36 tag-link-position-4\" style=\"font-size: 8pt;\" aria-label=\"Conference (1 item)\">Conference<\/a>\n<a href=\"https:\/\/nugene.com.cn\/en\/index.php\/tag\/cordycepin\/\" class=\"tag-cloud-link tag-link-22 tag-link-position-5\" style=\"font-size: 8pt;\" aria-label=\"Cordycepin (1 item)\">Cordycepin<\/a>\n<a href=\"https:\/\/nugene.com.cn\/en\/index.php\/tag\/coronavirus-vaccine\/\" class=\"tag-cloud-link tag-link-31 tag-link-position-6\" style=\"font-size: 8pt;\" aria-label=\"Coronavirus Vaccine (1 item)\">Coronavirus Vaccine<\/a>\n<a href=\"https:\/\/nugene.com.cn\/en\/index.php\/tag\/covid-19\/\" class=\"tag-cloud-link tag-link-30 tag-link-position-7\" style=\"font-size: 8pt;\" aria-label=\"COVID-19 (1 item)\">COVID-19<\/a>\n<a href=\"https:\/\/nugene.com.cn\/en\/index.php\/tag\/dntps\/\" class=\"tag-cloud-link tag-link-27 tag-link-position-8\" style=\"font-size: 8pt;\" aria-label=\"dNTPs (1 item)\">dNTPs<\/a>\n<a href=\"https:\/\/nugene.com.cn\/en\/index.php\/tag\/exhibition\/\" class=\"tag-cloud-link tag-link-37 tag-link-position-9\" style=\"font-size: 8pt;\" aria-label=\"Exhibition (1 item)\">Exhibition<\/a>\n<a href=\"https:\/\/nugene.com.cn\/en\/index.php\/tag\/gmp-site\/\" class=\"tag-cloud-link tag-link-28 tag-link-position-10\" style=\"font-size: 8pt;\" aria-label=\"GMP site (1 item)\">GMP site<\/a>\n<a href=\"https:\/\/nugene.com.cn\/en\/index.php\/tag\/immorna\/\" class=\"tag-cloud-link tag-link-24 tag-link-position-11\" style=\"font-size: 8pt;\" aria-label=\"Immorna (1 item)\">Immorna<\/a>\n<a href=\"https:\/\/nugene.com.cn\/en\/index.php\/tag\/investment\/\" class=\"tag-cloud-link tag-link-25 tag-link-position-12\" style=\"font-size: 8pt;\" aria-label=\"investment (1 item)\">investment<\/a>\n<a href=\"https:\/\/nugene.com.cn\/en\/index.php\/tag\/lnp\/\" class=\"tag-cloud-link tag-link-21 tag-link-position-13\" style=\"font-size: 8pt;\" aria-label=\"LNP (1 item)\">LNP<\/a>\n<a href=\"https:\/\/nugene.com.cn\/en\/index.php\/tag\/mrna\/\" class=\"tag-cloud-link tag-link-19 tag-link-position-14\" style=\"font-size: 22pt;\" aria-label=\"mRNA (5 items)\">mRNA<\/a>\n<a href=\"https:\/\/nugene.com.cn\/en\/index.php\/tag\/ntps\/\" class=\"tag-cloud-link tag-link-26 tag-link-position-15\" style=\"font-size: 8pt;\" aria-label=\"NTPs (1 item)\">NTPs<\/a>\n<a href=\"https:\/\/nugene.com.cn\/en\/index.php\/tag\/nucleosides\/\" class=\"tag-cloud-link tag-link-15 tag-link-position-16\" style=\"font-size: 8pt;\" aria-label=\"Nucleosides (1 item)\">Nucleosides<\/a>\n<a href=\"https:\/\/nugene.com.cn\/en\/index.php\/tag\/nucleotides\/\" class=\"tag-cloud-link tag-link-16 tag-link-position-17\" style=\"font-size: 8pt;\" aria-label=\"Nucleotides (1 item)\">Nucleotides<\/a>\n<a href=\"https:\/\/nugene.com.cn\/en\/index.php\/tag\/oligo\/\" class=\"tag-cloud-link tag-link-20 tag-link-position-18\" style=\"font-size: 8pt;\" aria-label=\"Oligo (1 item)\">Oligo<\/a>\n<a href=\"https:\/\/nugene.com.cn\/en\/index.php\/tag\/oligonucleotides\/\" class=\"tag-cloud-link tag-link-14 tag-link-position-19\" style=\"font-size: 8pt;\" aria-label=\"Oligonucleotides (1 item)\">Oligonucleotides<\/a>\n<a href=\"https:\/\/nugene.com.cn\/en\/index.php\/tag\/phosphoramidite\/\" class=\"tag-cloud-link tag-link-17 tag-link-position-20\" style=\"font-size: 8pt;\" aria-label=\"Phosphoramidite (1 item)\">Phosphoramidite<\/a>\n<a href=\"https:\/\/nugene.com.cn\/en\/index.php\/tag\/phosphoramidites\/\" class=\"tag-cloud-link tag-link-13 tag-link-position-21\" style=\"font-size: 8pt;\" aria-label=\"Phosphoramidites (1 item)\">Phosphoramidites<\/a>\n<a href=\"https:\/\/nugene.com.cn\/en\/index.php\/tag\/rna-sequences\/\" class=\"tag-cloud-link tag-link-10 tag-link-position-22\" style=\"font-size: 8pt;\" aria-label=\"RNA sequences (1 item)\">RNA sequences<\/a>\n<a href=\"https:\/\/nugene.com.cn\/en\/index.php\/tag\/solid-phase-synthesis\/\" class=\"tag-cloud-link tag-link-11 tag-link-position-23\" style=\"font-size: 8pt;\" aria-label=\"Solid-phase synthesis (1 item)\">Solid-phase synthesis<\/a>\n<a href=\"https:\/\/nugene.com.cn\/en\/index.php\/tag\/synthesis-of-oligonucleotides\/\" class=\"tag-cloud-link tag-link-12 tag-link-position-24\" style=\"font-size: 8pt;\" aria-label=\"synthesis of oligonucleotides (1 item)\">synthesis of oligonucleotides<\/a>\n<a href=\"https:\/\/nugene.com.cn\/en\/index.php\/tag\/vaccine\/\" class=\"tag-cloud-link tag-link-32 tag-link-position-25\" style=\"font-size: 8pt;\" aria-label=\"Vaccine (1 item)\">Vaccine<\/a><\/p>","protected":false},"excerpt":{"rendered":"<p>Mol Pharm .&nbsp;2015 Jun 1;12(6):2010-8.&nbsp;doi: 10.1021\/mp5008212.&nbsp;Epub 2015 Apr 28. D33-targeted lipid nanoparticles (aCD33LNs) were synthesized for delivery of GTI-2040, an antisense oligonucleotide (ASO) against the R2 subunit of ribonucleotide reductase, to acute myelogenous leukemia (AML). These LNs incorporated a deoxycholate-polyethylenimine (DOC-PEI) conjugate, which has shown significant activity to facilitate oligonucleotide delivery. Anti-CD33 scFv (aCD33) was &hellip;<\/p>\n<p class=\"read-more\"> <a class=\"\" href=\"https:\/\/nugene.com.cn\/en\/index.php\/lipid-nanoparticles-for-therapeutic-delivery-of-gti-2040\/\"> <span class=\"screen-reader-text\">Lipid Nanoparticles for Therapeutic Delivery of GTI-2040<\/span> Read More &raquo;<\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"closed","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"site-sidebar-layout":"default","site-content-layout":"default","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","theme-transparent-header-meta":"","adv-header-id-meta":"","stick-header-meta":"","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","footnotes":""},"categories":[1],"tags":[],"class_list":["post-309","post","type-post","status-publish","format-standard","hentry","category-product"],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v21.1 - 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