Optogenetic storage and release of protein and mRNA in live cells and animals

Chaeyeon Lee, Jeonghye Yu, Jongpil Shin, Jihwan Yu, Yungyeong Heo, Moosung Lee, Daseuli Yu (), YongKeun Park () and Won Do Heo ()
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Chaeyeon Lee: Korea Advanced Institute of Science and Technology (KAIST)
Jeonghye Yu: Korea Advanced Institute of Science and Technology (KAIST)
Jongpil Shin: Korea Advanced Institute of Science and Technology (KAIST)
Jihwan Yu: Korea Advanced Institute of Science and Technology (KAIST)
Yungyeong Heo: Korea Advanced Institute of Science and Technology (KAIST)
Moosung Lee: Korea Advanced Institute of Science and Technology (KAIST)
Daseuli Yu: KAIST
YongKeun Park: Korea Advanced Institute of Science and Technology (KAIST)
Won Do Heo: Korea Advanced Institute of Science and Technology (KAIST)

Nature Communications, 2025, vol. 16, issue 1, 1-14

Abstract: Abstract Cells compartmentalize biomolecules in membraneless structures called biomolecular condensates. While their roles in regulating cellular processes are increasingly understood, tools for their synthetic manipulation remain limited. Here, we introduce RELISR (Reversible Light-Induced Store and Release), an optogenetic condensate system that enables reversible storage and release of proteins or mRNAs. RELISR integrates multivalent scaffolds, optogenetic switches, and cargo-binding domains to trap cargo in the dark and release it upon blue-light exposure. We demonstrate its utility in primary neurons and show that light-triggered release of signaling proteins can modulate fibroblast morphology. Furthermore, light-induced release of cargo mRNA results in protein translation both in vitro and in live mice. RELISR thus provides a versatile platform for spatiotemporal control of protein activity and mRNA translation in complex biological systems, with broad potential for research and therapeutic applications.

Date: 2025
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DOI: 10.1038/s41467-025-61322-y

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