A genetically encoded device for transcriptome storage in mammalian cells

Amazing stuff!

"... Vaults — so named because early researchers likened them to vaulted cathedral ceilings — are enigmatic structures naturally occurring inside cells. Although smaller than the membrane-enclosed organelles such as the nucleus or mitochondria, vaults are the largest particles made by human cells and among the most abundant, with about 10,000 in most cells and up to 100,000 in some immune cells.

First discovered 40 years ago, their function remains unknown. Vaguely resembling footballs or hand grenades, vaults are mostly hollow — meaning they could be engineered to store other molecules. Better yet, they do not trigger an immune response because they already exist within cells. ...

The system uses poly(A) binding proteins, which naturally bind to mRNA and are widely employed to produce transcripts of gene activity. With bioengineering, researchers attached these proteins to others that naturally form vaults. When the vault takes shape and closes up, the transcript information becomes enclosed within. ...

The vaults act like protective containers and shield the RNA from normal degradation by enzymes.

In experiments, the researchers found that the TimeVaults extended RNA preservation more than sevenfold — from a half-life of about 17 hours in the cell cytoplasm to 132 hours inside the vaults.

This information is even inherited by daughter cells. When cells divide, the vaults are divided between the offspring cells.

Next, researchers used chemical techniques to dissolve the vaults and assemble transcriptome snapshots of past activity, which can be compared with other snapshots taken later. ..."

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."

Why did that cancer cell become drug-resistant? — Harvard Gazette "Researchers find way to create microscopic archives of gene activity to gain insights into how, why changes happen"

A genetically encoded device for transcriptome storage in mammalian cells (no public access)