Promising non-viral vector for efficient and versatile delivery of mRNA for antigen-specific immunotherapy

Rebuma Firdessa-Fite, Jorge Postigo-Fernandez, Valérie Toussaint-Moreau, Fabrice Stock, Alengo Nyamay'Antu, Patrick Erbacher, Rémi J Creusot
2020 Cell and Gene Therapy Insights  
Cellular immunotherapy involves the modification of immune cells in vivo or ex vivo to elicit, modulate or suppress immune responses. Modification by mRNA has become an attractive alternative to DNA vectors as a non-viral delivery approach, due to high transfection efficiency including in non-dividing cells. However, widespread adoption of this strategy is currently limited by the lack of commercially available ready-to-use reagents for in vivo delivery of mRNA. In this study, we evaluate the
more » ... wly launched in vivo-jetRNA ® for the delivery of mRNA-encoded antigens into nanoparticles and the resulting CD4 + T cell responses to one of the expressed epitopes. Four routes of administration were compared to determine the in vivo biodistribution of the nanoparticles based on evidence of antigen-specific T cell responses in various lymphoid tissues. Systemic routes achieved efficient delivery with most antigen-specific T cells stimulated in all sites tested. In the case of local routes, responses were confined to draining lymph nodes. Some of the activation markers (CD25, PD-1) were only induced in specific sites using specific routes, suggesting a role for the local dose of nanoparticles and the nature of antigen-presenting cells present involved in different sites. When applied to splenocytes from different mouse strains in vitro, the mRNA nanoparticles had marginal effect on the maturation of antigen-presenting cells, did not negatively affect viability and did not induce proinflammatory cytokines. We conclude that in vivo-jetRNA ® is a promising mRNA formulation for efficient delivery of genes and antigens in vivo. Disclosure and potential conflicts of interest: Rémi J Creusot is the inventor of the Endotope platform for optimal presentation of nucleic acid-encoded epitopes (US20170283810).
doi:10.18609/cgti.2020.154 fatcat:jvovy73dgvckbkhcqjvr7qjb4q