Amazing stuff!
"By converting a natural cell component called a vault into an mRNA time capsule, researchers have identified — and blocked — some of the mysterious gene activity that allows cancer cells to resist targeted drugs. These capsules, named ‘TimeVaults’, can grab onto a small amount of mRNA and store it for more than a week. Analyzing the contents of these capsules revealed some of the genetic drivers behind drug-resistant lung cancer cells known as persistors. When some overly active genes inside these cancer cells were inhibited, drugs became more effective against them."
"... To turn vaults into time capsules, Chen’s team engineered a vault protein in such a way that it recognizes and links to a molecular hallmark of mRNA molecules, thereby capturing the mRNA inside the vault. The production of this protein — the equivalent of hitting the ‘record’ button — is triggered by treating cells with a drug and stopped by withdrawing the drug.
With these modifications, the TimeVaults captured a small fraction of all of the mRNA molecules produced by a human cell line throughout a 24-hour period, and stored them for at least a week, ... The researchers found no sign that cells with TimeVaults behaved differently from regular vaults because of their cargo, nor that the barrel-shaped structures changed shape or size once filled ..."
From the 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."
A ‘time capsule’ for cells stores the secret experiences of their past "Scientists have transformed enigmatic cell structures, called vaults, into storage units for messenger RNA molecules." (no public access)
A genetically encoded device for transcriptome storage in mammalian cells (no public access)
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