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Marţi, 23 Octombrie 2018 EET
 
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Designul rational al unui vaccin terapetic anti HIV-1 bazat pe o formula inovativa de ARNm inglobat in nanoparticule/ Rationally designed therapeutic vaccine against HIV-1 based on a novel formulation of nanoparticle-protected mRNA” (HIV-NANOVA)

Rezumat:

Date recente au demonstrat ca vaccinuri terapeutice bazate pe celule dendritice (DC) pot controla infectia HIV. Totusi, aplicarea acestor vaccinuri pe scara larga si comercializarea lor este impiedicata de necesitatea individualizarii in functie de pacient, de cerintele legate de existenta unei infrastructuri specializate, de un nivel inalt de expertiza necesar prepararii DC si de conditiile speciale de stocare si transport. Din aceste motive, sunt necesare noi vaccinuri candidat, care sa pastreze calitatile unui vaccin bazat pe DC si sa depaseasca limitarile acestora. Vaccinurile bazate pe ARNm par promitatoare in acest sens. A fost demonstrat ca ARNm este preluat selectiv de DC dupa injectare in ganglioni limfatici si induce un puternic raspuns imun, specific pentru antigenul codificat. De aceea, un vaccin candidat interesant poate fi reprezentat de un ARNm capabil sa livreze catre DC atat o secventa antigenica inalt conservata a HIV, cat si semnale activatorii potente. O limitare importanta a unei asemenea abordari este legata de necesitatea inocularii intraganglionare, greu de realizat in practica clinica; de aceea se impune explorarea unor cai alternative, standardizate, de administrare a vaccinului. In plus se ridica problema protectiei ARNm, in mod inerent expus la actiunea RN-azelor ambientale. Tinand cont de aceste premize, proiectul de fata va evalua fezabilitatea unui vaccin terapeutic anti HIV-1 bazat pe o formula inovativa de ARNm,  inglobat, prin intermediul unui polimer de acid polilactic derivat din lizina, in nanoparticule biodegradabile.

 

Abstract engleza

Recent data demonstrate the feasibility of dendritic cell based therapeutic vaccines to control HIV-1 infection.  Nevertheless, their patient specific nature, the specialized infrastructure, the high level of expertise required for preparation and the high demands for storage and transportation preclude widespread application and commercialization.  Therefore novel vaccine candidates that retain the power of a DC-based vaccine but at the same time overcome its limitations need to be developed. mRNA-based vaccines offer significant promise in this respect.  It was shown that mRNA is selectively taken up by dendritic cells upon injection in the lymph node and induces strong antigen specific immune responses.  Therefore, an interesting vaccine candidate could be an mRNA-based vaccine able to deliver both a rationally designed HIV antigen sequence and on the other hand potent activation signals.  An important drawback of this approach is the fact that intranodal immunization is not easily applicable in clinical settings.  Therefore, more standardized routes of administration need to be explored.  Given the inherent sensitivity of RNA to ambient RNases, these approaches will require protection of mRNA.  In this project we will evaluate the feasibility of delivering an mRNA based therapeutic vaccine with biodegradable nanoparticles loaded with RNA entrapped at their surface through a lysine-derived poly-lactic acid based polymer.

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