{"id":217467,"date":"2025-07-09T14:03:48","date_gmt":"2025-07-09T19:03:48","guid":{"rendered":"https:\/\/lifeboat.com\/blog\/2025\/07\/efficient-mrna-delivery-to-resting-t-cells-to-reverse-hiv-latency"},"modified":"2025-07-09T14:03:48","modified_gmt":"2025-07-09T19:03:48","slug":"efficient-mrna-delivery-to-resting-t-cells-to-reverse-hiv-latency","status":"publish","type":"post","link":"https:\/\/lifeboat.com\/blog\/2025\/07\/efficient-mrna-delivery-to-resting-t-cells-to-reverse-hiv-latency","title":{"rendered":"Efficient mRNA delivery to resting T cells to reverse HIV latency"},"content":{"rendered":"<p><a class=\"aligncenter blog-photo\" href=\"https:\/\/lifeboat.com\/blog.images\/efficient-mrna-delivery-to-resting-t-cells-to-reverse-hiv-latency.jpg\"><\/a><\/p>\n<p>A major hurdle to curing HIV is the persistence of integrated proviruses in resting CD4+ T cells that remain in a transcriptionally silent, latent state. One strategy to eradicate latent HIV is to activate viral transcription, followed by elimination of infected cells through virus-mediated cytotoxicity or immune-mediated clearance. We hypothesised that mRNA-lipid nanoparticle (LNP) technology would provide an opportunity to deliver mRNA encoding proteins able to reverse HIV latency in resting CD4+ T cells. Here we develop an LNP formulation (LNP X) with unprecedented potency to deliver mRNA to hard-to-transfect resting CD4+ T cells in the absence of cellular toxicity or activation. Encapsulating an mRNA encoding the HIV Tat protein, an activator of HIV transcription, LNP X enhances HIV transcription in ex vivo CD4+ T cells from people living with HIV. LNP X further enables the delivery of clustered regularly interspaced short palindromic repeats (CRISPR) activation machinery to modulate both viral and host gene transcription. These findings offer potential for the development of a range of nucleic acid-based T cell therapeutics.<\/p>\n<hr>\n<p>Resting T cells are difficult to manipulate, and are a reservoir for latent HIV. Here, the authors develop a lipid nanoparticle formulation with the ability to transfect resting primary human T cells, enabling delivery of mRNAs that result in reactivation of latent HIV. This could help development of HIV cure strategies.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>A major hurdle to curing HIV is the persistence of integrated proviruses in resting CD4+ T cells that remain in a transcriptionally silent, latent state. One strategy to eradicate latent HIV is to activate viral transcription, followed by elimination of infected cells through virus-mediated cytotoxicity or immune-mediated clearance. We hypothesised that mRNA-lipid nanoparticle (LNP) technology [\u2026]<\/p>\n","protected":false},"author":534,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[11,4],"tags":[],"class_list":["post-217467","post","type-post","status-publish","format-standard","hentry","category-biotech-medical","category-nanotechnology"],"_links":{"self":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/posts\/217467","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\/534"}],"replies":[{"embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/comments?post=217467"}],"version-history":[{"count":0,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/posts\/217467\/revisions"}],"wp:attachment":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/media?parent=217467"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/categories?post=217467"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/tags?post=217467"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}