In Cellulo and In Vivo Comparison of Cholesterol, Beta-Sitosterol and Dioleylphosphatidylethanolamine for Lipid Nanoparticle Formulation of mRNA - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Nanomaterials Année : 2022

In Cellulo and In Vivo Comparison of Cholesterol, Beta-Sitosterol and Dioleylphosphatidylethanolamine for Lipid Nanoparticle Formulation of mRNA

Résumé

Lipid Nanoparticles (LNPs) are a leading class of mRNA delivery systems. LNPs are made of an ionizable lipid, a polyethyleneglycol (PEG)-lipid conjugate and helper lipids. The success of LNPs is due to proprietary ionizable lipids and appropriate helper lipids. Using a benchmark lipid (D-Lin-MC3) we compared the ability of three helper lipids to transfect dendritic cells in cellulo and in vivo. Studies revealed that the choice of helper lipid does not influence the transfection efficiency of immortalized cells but, LNPs prepared with DOPE (dioleylphosphatidylethanolamine) and β-sitosterol were more efficient for mRNA transfection in murine dendritic cells than LNPs containing DSPC (distearoylphosphatidylcholine). This higher potency of DOPE and β-sitosterol LNPs for mRNA expression was also evident in vivo but only at low mRNA doses. Overall, these data provide valuable insight for the design of novel mRNA LNP vaccines.
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Dates et versions

hal-03727652 , version 1 (10-10-2022)

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Ayoub Medjmedj, Albert Ngalle-Loth, Rudy Clemençon, Josef Hamacek, Chantal Pichon, et al.. In Cellulo and In Vivo Comparison of Cholesterol, Beta-Sitosterol and Dioleylphosphatidylethanolamine for Lipid Nanoparticle Formulation of mRNA. Nanomaterials, 2022, 12 (14), pp.2446. ⟨10.3390/nano12142446⟩. ⟨hal-03727652⟩
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