ApoE2-DARPin fusion proteins enable selective RNA transfer to CD8 T cells by lipid nanoparticles

RNA-LNPs targeted to CD8-positive T lymphocytes successfully labeled a substantial fraction of these cells in humanized mice and donor blood.

• RNA-LNPs exhibit a broad ability to enter various cell types, primarily utilizing the low-density lipoprotein receptor for cell entry.
• DARPins, which have a high affinity for CD8, were genetically fused to apolipoprotein E2 to create targeted RNA-LNPs.
• The targeted RNA-LNPs effectively distinguished between CD8-positive and CD8-negative T cells in both mouse and human samples.
• In experiments, these targeted nanoparticles showed minimal binding to CD4+ T cells, indicating specificity for CD8+ T cells.
• The findings suggest that the ApoE2-DARPin proteins stay associated with RNA-LNPs in serum, offering a new biological engineering approach for precise targeting.

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