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Spatial profiling of pooled mRNA-LNP delivery in vivo with NanoSTAMP

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.

2026-08-26 bioengineering
10.64898/2026.08.25.746710 bioRxiv
Show abstract

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.

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