A genetically encoded device for transcriptome storage in mammalian cells 2025 Chen et al

Andy

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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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"Researchers have engineered a time capsule for cells, capable of collecting and storing mementos of past activity.

The cellular storage units, called TimeVaults, could help unlock secrets to cancer-drug resistance and stem-cell biology, and more broadly how past events shape a cell’s future. The findings were published today in Science, https://www.nature.com/articles/d41586-026-00116-8#ref-CR11.

TimeVaults are made from mysterious cell structures called vaults, which have been modified to collect and store the molecular products of gene transcription, known as messenger RNA (mRNA) molecules.

“This is a major step towards a longstanding goal in the field: being able to continuously record transcription in human cells,” says Randall Platt, a biological engineer at the Swiss Federal Institute for Technology in Zurich. “I anticipate that TimeVaults will allow us to observe facets of biology previously inaccessible to us.”"

Article in Nature
 
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