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January 17, 2026Science11 citations

A genetically encoded device for transcriptome storage in mammalian cells

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YCYu-Kai ChaoMWMichelle WuQGQiyu Gong

Key Points

  • The aim is to develop a system that links past cellular states to future outcomes by recording transcriptomes in living cells.
  • Developed TimeVault, a genetically encoded system for transcriptome storage.
  • Utilized engineered vault particles to capture mRNA.
  • Assessed stability of stored transcriptomes over 7 days in living cells.
  • TimeVault successfully recorded transcriptomes with minimal cellular perturbation.
  • Stored transcriptomes showed stability for over a week.
  • Captured gene expression changes related to stress responses in lung cancer cells.

Abstract

Understanding how cells make decisions over time requires the ability to link past molecular states to future phenotypic outcomes. We present TimeVault, a genetically encoded system that records and stores transcriptomes within living mammalian cells for future readout. TimeVault leverages engineered vault particles that capture mRNA through poly(A) binding protein. We demonstrate that the transcriptome stored by TimeVaults is stable in living cells for over 7 days. TimeVault enables high-fidelity transcriptome-wide recording with minimal cellular perturbation, capturing transient stress responses and revealing gene expression changes underlying drug-naive persister states in lung cancer cells that evade EGFR inhibition. By linking past and present cellular states, TimeVault provides a powerful tool for decoding how cells respond to stress, make fate decisions, and resist therapy.

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Cite This Study

Chao et al. (2026) studied this question.

synapsesocial.com/papers/696b25f3d2a12237a93494b7https://doi.org/10.1126/science.adz9353
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