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Non-viral delivery of self-amplifying RNA

Geall, Andrew and Verma, Ayush and Otten, Gillis and Shaw, Christine and Hekele, Armin and Banerjee, Kaustuv and Beard, Clayton and Cu, Yen and Brito, Luis and Krucker, Thomas and O'Hagan, Derek and Singh, Manmohan and Mason, Peter and Valiante, Nicholas and Dormitzer, Philip and Barnett, Susan and Rappuoli, Rino and Ulmer, Jeffrey and Mandl, Christian (2012) Non-viral delivery of self-amplifying RNA. PNAS (Proceedings of the National Academy of Sciences), 109 (36). pp. 14604-14609. ISSN 1091-6490

Abstract

Despite two decades of research on nucleic acid vaccines, there is still no commercial product for human use. Taking advantage of the recent innovations around systemic delivery of siRNA using lipid nanoparticles (LNPs), we developed a self-amplifying RNA vaccine. Here we show that delivery of a 9 kb self-amplifying RNA encapsulated within an LNP substantially increased immunogenicity compared to delivery of naked RNA. This novel vaccine technology was tested with genes encoding antigens from several viral pathogens and found to elicit broad and potent immune responses. Humoral and cellular immune responses were comparable to a viral delivery technology (without the inherent limitations of viral vectors) and superior to plasmid DNA (pDNA) delivered using electroporation (EP). Our results suggest that a comprehensive evaluation of non-viral technologies to deliver self-amplifying RNA vaccines is warranted.

Item Type: Article
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Additional Information: approval through V&D, head of research has given ok - see below The email below indicates that the Global Head of Vaccines Research is ready to submit the paper. Andy From: RAPPUOLI, RINO Sent: Monday, February 27, 2012 1:49 AM To: Geall, Andrew; Mandl, Christian; Ulmer, Jeffrey; Barnett, Susan; Dormitzer, Philip; Valiante, Nicholas; Mason, Peter; Singh, Manmohan; OHagan, Derek; Krucker, Thomas; Brito, Luis; Beard, Clayton; Cu, Yen (Ext); Banerjee, Kaustuv (Ext); Hekele, Armin; Shaw, Christine; Otten, Gillis; Verma, Ayush Subject: RE: Last round of edits to the Nature Medicine manuscript Excellent work For me it is ready to go Ciao, Rino From: Geall, Andrew Sent: giovedì 23 febbraio 2012 12.50 To: Mandl, Christian; Ulmer, Jeffrey; RAPPUOLI, RINO; Barnett, Susan; Dormitzer, Philip; Valiante, Nicholas; Mason, Peter; Singh, Manmohan; OHagan, Derek; Krucker, Thomas; Brito, Luis; Beard, Clayton; Cu, Yen (Ext); Banerjee, Kaustuv (Ext); Hekele, Armin; Shaw, Christine; Otten, Gillis; Verma, Ayush Subject: Last round of edits to the Nature Medicine manuscript Dear All, Please find attached the latest version of the manuscript. I hope we will get internal clearance to submit to Nature Medicine on Friday of this week. The intension is then to submit early next week, giving everybody the weekend to take a final look at the manuscript. Things to note 1. If you want a middle initial in your name please add 2. I have included the figure legends on the PowerPoint slides for ease of reading, but if you want to add comments or edits to the legend, please add these to the word document Many thanks to all for getting this ready! Andy
Keywords: vaccine, self-amplifying, RNA, LNP
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Date Deposited: 13 Oct 2015 13:14
Last Modified: 13 Oct 2015 13:14
URI: https://oak.novartis.com/id/eprint/7302

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