The future of genetic medicines delivered via targeted lipid nanoparticles to leukocytes

Genetic medicines hold vast therapeutic potential, offering the ability to silence or induce gene expression, knock out genes, and even edit DNA fragments. Applying these therapeutic modalities to leukocytes offers a promising path for treating various conditions yet overcoming the obstacles of specific and efficient delivery to leukocytes remains a major bottleneck in their clinical translation. Lipid nanoparticles (LNPs) have emerged as the leading delivery system for nucleic acids due to their remarkable versatility and ability to improve their in vivo stability, pharmacokinetics, and therapeutic benefits. Equipping LNPs with targeting moieties can promote their specific cellular uptake and internalization to leukocytes, making targeted LNPs (tLNPs) an inseparable part of developing leukocyte-targeted gene therapy. However, despite the significant advancements in research, genetic medicines for leukocytes using targeted delivery approaches have not been translated into the clinic yet. Herein, we discuss the important aspects of designing tLNPs and highlight the considerations for choosing an appropriate bioconjugation strategy and targeting moiety. Furthermore, we provide our insights on limiting challenges and identify key areas for further research to advance these exciting therapies for patient care.