Existing pooled lipid nanoparticle (LNP) screens lack spatial information on formulation localization, cellular uptake, and associated multicellular tissue responses. Here we introduce NanoSTAMP, a spatially resolved, pooled in vivo screening platform for barcoded LNP libraries that uses fluorescence in situ hybridization (FISH)-based barcode readout and is compatible with spatial omics. NanoSTAMP links LNP formulation to cell-type specific uptake, cargo expression, and nearby multicellular neighborhoods within intact tissue, which enables spatially-informed design of RNA delivery, establishing tissue architecture as a dimension of LNP performance.
Zhu, Y., Miao, Y., Anderson, I. J., Li, Y., Aghnatios, B., No, J., Ma, J., Yu, D., Wei, C., Lu, X., Wang, J., van de Klashorst, J., Mao, H.-Q., Hickey, J. W.
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