LipiGo: A Versatile DNA-Lipid Nanoparticle Hybrid for Precision Drug Delivery

Kadletz, K.; Kimna, C.; Reichenbach, V. K.; Carofiglio, O.; Jeridi, D.; Hu, S.; Khalin, I.; Grzejdak, J.; Chen, Y.; Horvath, I.; Minde, D.-P.; Ali, M.; Sych, T.; Hoeher, L.; Aydeniz, E.; Kulcu, Y. A.; Ricci, A.; Liesz, A.; Sezgin, E.; Ussar, S.; Hellal, F.; Elsner, M.; Erturk, A.

doi:10.1101/2025.09.15.676334

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bioRxiv · 10.1101/2025.09.15.676334

LipiGo: A Versatile DNA-Lipid Nanoparticle Hybrid for Precision Drug Delivery

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Abstract

Lipid nanoparticles (LNPs) are established carriers for nucleic acid delivery, however, achieving efficient delivery to non-hepatic tissues remains a major challenge. Here, we present LipiGo, a nanocarrier platform engineered by integrating short single stranded DNA molecules into the lipid nanoparticle structure. Using whole body tissue clearing, advanced imaging and AI-based analysis, we show that LipiGo redirects functional mRNA delivery to lymphoid organs, particularly the spleen. Immune cell profiling further reveals enhanced uptake within key immune populations, including antigen-presenting cells, compared to standard LNPs. Beyond passive redistribution, LipiGo leverages DNA hybridization to enable modular attachment of targeting ligands for active targeting as demonstrated by cell-specific delivery to white adipocytes. Overall, the dual-purpose design principle of LipiGo demonstrates high modularity and efficiency, enabling tissue and cell specific delivery beyond hepatic applications. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=100 SRC="FIGDIR/small/676334v2_ufig1.gif" ALT="Figure 1"> View larger version (45K): org.highwire.dtl.DTLVardef@9b69eorg.highwire.dtl.DTLVardef@1b45bd0org.highwire.dtl.DTLVardef@1f7b79dorg.highwire.dtl.DTLVardef@37a673_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Kadletz, K., Kimna, C., Reichenbach, V. K., Carofiglio, O., Jeridi, D., Hu, S., Khalin, I., Grzejdak, J., Chen, Y., Horvath, I., Minde, D.-P., Ali, M., Sych, T., Hoeher, L., Aydeniz, E., Kulcu, Y. A., Ricci, A., Liesz, A., Sezgin, E., Ussar, S., Hellal, F., Elsner, M., Erturk, A.. 2025-09-18. LipiGo: A Versatile DNA-Lipid Nanoparticle Hybrid for Precision Drug Delivery. https://doi.org/10.1101/2025.09.15.676334

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