Stability of Cryo-Concentrated Complexes

Härk, Heleri Heike; Porosk, Ly; Arukuusk, Piret; Kurrikoff, Kaido

doi:10.17952/36eps/36eps.2022.165

Cited by 1 publication

(1 citation statement)

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“…This pushed us to find a more suitable method. Inspired by our previous work on cryo-concentration of complexes [ 21 ] and the stability of NF55/pDNA complexes [ 26 ], we tested whether the freeze-drying of already formed complexes would help to preserve their activity. Encouragingly, this time the efficacy was retained for one-day complexes and we observed similar luciferase expression in the spleens as with freshly formed mRNA complexes ( Figure 4 d).…”

Section: Resultsmentioning

confidence: 99%

The Development of Cell-Penetrating Peptides for Efficient and Selective In Vivo Expression of mRNA in Spleen Tissue

et al. 2023

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mRNA-based therapeutics are presently one of the nucleic acid-based therapeutics with a high potential for extraordinary success as preventive vaccines. Current applications with mRNA therapeutics rely on lipid nanoparticle (LNP) mediated delivery of nucleic acids. In order to achieve the transition from preventive to therapeutic vaccines, there is a challenge of delivering the mRNA into non-hepatic tissues, especially into lymphoid tissues such as the spleen and lymph nodes. In this work, we characterize new cell-penetrating peptides NF424 and NF436 that exhibit preferential delivery of mRNA into the spleen after a single i.v. injection, without the use of any active targeting mechanisms. We show that between the spleen, liver, and the lungs, >95% of mRNA expression arises in the spleen tissue and the majority of expression occurs in the dendritic cells. The cell-penetrating peptides NF424 and NF436 represent promising candidates for cancer immunotherapeutic applications with tumor antigens.

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Section: Resultsmentioning

confidence: 99%