Teko-Agbo Clémentine Ayélé, Josse Emilie, Konate Karidia, Deshayes Sébastien, de Santa Barbara Pascal, Faure Sandrine, Boisguérin Prisca, Vivès Eric
PhyMedExp, University of Montpellier, INSERM, CNRS, Montpellier, France.
CHU Arnaud de Villeneuve, 371 Avenue du Doyen G. Giraud, Montpellier, France.
Mol Ther Nucleic Acids. 2025 Jul 29;36(3):102650. doi: 10.1016/j.omtn.2025.102650. eCollection 2025 Sep 9.
Nucleic acid molecules are emerging as potential therapeutic tools, as evidenced by the transfection of small interfering RNA (siRNA) molecules in therapeutic applications and messenger RNAs in immunotherapeutic vaccination. In most cases, these nucleic acids are conditioned as lipid nanoparticles made with different lipid moieties to promote their intracellular delivery. Over the past few years, we have documented the delivery of siRNAs using a single short (15 amino acids) peptide called WRAP5, which follows an extremely simplified formulation phase that enables the formation of nanoparticles with a diameter of 60-80 nm. We indeed demonstrated the expected dose-response reduction in the levels of the targeted proteins. To apply this technology to the cellular delivery of mRNAs, we investigated the ability of the WRAP5 peptide to transfect mRNAs of different sizes and promote the expression of their proteins. These peptide-based nanoparticles, which also have diameters ranging from 60 to 80 nm, showed remarkable stability over time when simply stored at 4°C and fully retained their transfection properties for up to several months post-formulation. Interestingly, we demonstrated that these nanoparticles were able to induce an immune response against the protein synthesized from the vectorized mRNA.
核酸分子正成为潜在的治疗工具，治疗应用中的小干扰RNA（siRNA）分子转染以及免疫治疗疫苗接种中的信使RNA都证明了这一点。在大多数情况下，这些核酸被制备成由不同脂质部分组成的脂质纳米颗粒，以促进其细胞内递送。在过去几年中，我们记录了使用一种名为WRAP5的单一短肽（15个氨基酸）递送siRNA的情况，该肽遵循极其简化的制剂阶段，能够形成直径为60-80nm的纳米颗粒。我们确实证明了靶向蛋白水平出现了预期的剂量反应降低。为了将这项技术应用于mRNA的细胞递送，我们研究了WRAP5肽转染不同大小mRNA并促进其蛋白表达的能力。这些基于肽的纳米颗粒直径也在60至80nm之间，当简单地保存在4°C时，随着时间的推移显示出显著的稳定性，并且在制剂后长达数月内完全保留其转染特性。有趣的是，我们证明这些纳米颗粒能够诱导针对载体化mRNA合成的蛋白的免疫反应。
