Mechanically-mediated low-pressure cell membrane poration enables tunable intracellular delivery of traditionally impermeable cargoes in high throughput and clinical scale formats
Hirsch, S. M.; Kreienberg, D.; Song, Z.; Larocque, A.; Zuo, Y.; Conover, R.; Jaecklein, E.; Gonzalez, K.; Imchen, A.; Franco, S.; Evans, M. A.; Wesselhoeft, R. A.; Swiatnicki, M. R.; Zegzouti, H.; Chesnov, K.; Wernig, M.; Dhawan, N. S.; Pye, C.; Loughhead, S. M.; Hanson, J. L. S.; Barclay, A.; Sharei, A.
Show abstract
Traditional intracellular delivery methods suffer from cargo inefficiencies, non-linear delivery kinetics, and cellular trauma. We designed a mechanically-mediated poration platform governed by deterministic, passive diffusion operating at low pressure which enables dose-dependent, cargo-agnostic intracellular delivery and preserves cellular homeostasis; key advantages include high-fidelity multiplexing, transient cell engineering, and direct-to-biology live-cell target engagement enabling development of novel intracellular delivery applications across drug discovery and cell therapy. We demonstrate examples including live-cell DEL discovery and MOA studies, complex and rapid cell therapy manufacturing, and assay development in sensitive primary cell types.
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