{"id":243554,"date":"2026-09-03T01:12:23","date_gmt":"2026-09-03T06:12:23","guid":{"rendered":"https:\/\/lifeboat.com\/blog\/2026\/09\/cell-factories-that-manufacture-microvesicles-containing-gene-silencing-rna-prodrugs"},"modified":"2026-09-03T01:12:23","modified_gmt":"2026-09-03T06:12:23","slug":"cell-factories-that-manufacture-microvesicles-containing-gene-silencing-rna-prodrugs","status":"publish","type":"post","link":"https:\/\/lifeboat.com\/blog\/2026\/09\/cell-factories-that-manufacture-microvesicles-containing-gene-silencing-rna-prodrugs","title":{"rendered":"Cell factories that manufacture microvesicles containing gene silencing RNA prodrugs"},"content":{"rendered":"

<\/a><\/p>\n

Precise and reversible suppression of gene expression by antisense RNA sequences is a strategy that is widely used in both basic research and clinical medicine (for reviews, see 1\u20133<\/a>). Naked or unmodified antisense RNA is rapidly degraded in biological fluids and is inefficiently internalized by cells (4<\/a>, 5<\/a>). Consequently, antisense RNAs used to silence gene expression have been delivered by encapsulating them extracellularly in lipid-based or gold-based nanoparticles (6<\/a>, 7<\/a>) or in vesicles released from cells grown in culture (8\u201311<\/a>). However, consistent and quantitatively reproducible RNA encapsulation in particles formed extracellularly has been a challenge (12<\/a>, 13<\/a>).<\/p>\n

Arrestin domain\u2013containing 1 (ARRDC1)-mediated microvesicles (ARMMs) are a naturally occurring distinct subclass of extracellular vesicles (EVs) that are uniquely dependent on the production of the arrestin-like cellular protein ARRDC1, and which\u2014unlike other vesicles released from cells\u2014are formed by outward budding of cytoplasmic membranes (14<\/a>). During ARMMs formation, the ARRDC1 protein is attached to ARMMs membranes and is loaded into ARMMs\u2014carrying along other macromolecules linked to it (14<\/a>, 15<\/a>). ARMMs can fuse with the plasma membranes of cells they encounter, and ARMMs cargos are discharged directly into the cytosol of recipient cells instead of being internalized by endocytosis\u2014thus avoiding degradative actions of endosomal enzymes (14<\/a>, 15<\/a>). Collectively, these properties have prompted investigation of ARMMs\u2019 abilities to deliver biologically manufactured macromolecules intercellularly (15\u201317<\/a>).<\/p>\n

Here, we describe and test a platform that synthesizes short hairpin RNA (shRNA) prodrugs as biochemically inert modules that are protected from RNA processing and degradation during their production and loading into ARMMs, but which become active gene-silencing agents upon delivery to recipient cells.<\/p>\n","protected":false},"excerpt":{"rendered":"

Precise and reversible suppression of gene expression by antisense RNA sequences is a strategy that is widely used in both basic research and clinical medicine (for reviews, see 1\u20133). Naked or unmodified antisense RNA is rapidly degraded in biological fluids and is inefficiently internalized by cells (4, 5). Consequently, antisense RNAs used to silence gene [\u2026]<\/p>\n","protected":false},"author":662,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[11,19,4],"tags":[],"class_list":["post-243554","post","type-post","status-publish","format-standard","hentry","category-biotech-medical","category-chemistry","category-nanotechnology"],"_links":{"self":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/posts\/243554","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/users\/662"}],"replies":[{"embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/comments?post=243554"}],"version-history":[{"count":0,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/posts\/243554\/revisions"}],"wp:attachment":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/media?parent=243554"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/categories?post=243554"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/tags?post=243554"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}