A genetically encoded device for transcriptome storage in mammalian cells

Science. 2026 Mar 26;391(6792):eadz9353. doi: 10.1126/science.adz9353. Epub 2026 Mar 26.

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 messenger RNA through polyadenosine [poly (A)]-binding protein. We demonstrate that the transcriptome stored by TimeVaults is stable in living cells for more than 7 days. TimeVault enables high-fidelity transcriptome-wide recording with minimal cellular perturbation, capturing transient stress responses and revealing gene expression changes underlying drug-naïve persister states in lung cancer cells that evade epidermal growth factor receptor (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.

MeSH terms

  • ErbB Receptors / antagonists & inhibitors
  • HEK293 Cells
  • Humans
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / genetics
  • RNA, Messenger* / genetics
  • RNA, Messenger* / metabolism
  • Transcriptome*

Substances

  • EGFR protein, human
  • ErbB Receptors
  • RNA, Messenger