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

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. Competing Interest Statement K.Kadletz, C.Kimna and A.Erturk have filed for intellectual property on the hybrid nanoparticles described herein. A.Erturk. is a co-founder of Deep Piction. The other authors declare no competing interests. Footnotes author affiliations updated; graphical abstract added