RNA sequencing is one of the most powerful ways to measure which genes are active in cells. However, most traditional RNA sequencing methods require cells to be broken open or chemically fixed before their RNA can be analyzed. That means researchers usually get only a single snapshot, rather than being able to follow the same living cells over time.

Researchers at Helmholtz Munich and the Technical University of Munich have developed a new approach called non-destructive transcriptomics by vesicular export, or NTVE. The method allows cells to release RNA information into the surrounding liquid through engineered virus-like particles, making it possible to monitor gene expression repeatedly without destroying the cells.

The basic idea is to turn living cells into ongoing reporters of their own activity. Instead of collecting RNA by lysing the cells, NTVE packages RNA barcodes or endogenous transcripts into small vesicle-like particles that can be collected from the cell culture medium. These exported RNA molecules can then be analyzed using standard RNA sequencing workflows.

This is important because many biological processes unfold over time. Stem cell differentiation, drug responses, genetic perturbations, and disease-related changes are all dynamic. With conventional RNA sequencing, researchers often need to sacrifice different groups of cells at different time points. NTVE makes it possible to follow RNA expression changes in the same cell population across multiple time points.

The researchers showed that NTVE could export endogenous transcripts from human and mouse cell lines with strong agreement to conventional lysate-derived RNA sequencing. They also used the approach to track changes after genetic and chemical perturbations, showing that the method can capture meaningful shifts in cell state.

One especially promising application is stem cell biology. The team used NTVE to monitor human induced pluripotent stem cell differentiation through daily, non-destructive transcriptomic profiling. This type of repeated measurement could help researchers better understand how cells transition into different lineages and how those transitions can be controlled.

NTVE can also be adapted for more than monitoring. By adding fusogens, the system can deliver mRNA-encoded effectors or ribonucleoprotein gene editors from sender cells to recipient cells, expanding its potential use in studies of cell communication and gene editing.

Overall, NTVE offers a new way to study living cells over time while preserving them for continued observation. By pairing vesicular export with RNA sequencing, researchers gain a more dynamic view of gene activity, which may be useful for stem cell research, drug testing, disease modeling, and other areas where timing matters.