New Protocol Boosts RNA Yields from Human Lung Tissue Slices

A team of scientists has unveiled an improved laboratory technique that markedly increases the amount and quality of RNA that can be extracted from precision‑cut lung slices, a model that retains the organ’s native cellular complexity while being studied outside the body.

Precision‑cut lung slices (PCLS) are thin sections of fresh human lung tissue that preserve the intricate architecture of airways, blood vessels and immune cells. Because the slices remain viable for days, researchers use them to explore disease mechanisms, test inhaled drugs, and investigate responses to viral infections without relying on animal models.

However, the very material that stabilizes lung tissue during slicing—typically a low‑melting agarose or similar hydrogel—has long hampered downstream molecular work. The polymer can trap nucleic acids and inhibit the chemicals used in standard extraction kits, resulting in low RNA yields and degraded samples that are unsuitable for high‑resolution gene‑expression studies.

To address this bottleneck, the investigators refined the lysis step by incorporating a brief enzymatic digestion that breaks down the embedding matrix, followed by a modified buffer system that protects RNA from degradation. In side‑by‑side comparisons, the new workflow produced up to three times more intact RNA than conventional methods, with integrity scores well within the range required for next‑generation sequencing.

The enhanced RNA recovery opens the door for more detailed transcriptomic profiling of PCLS, including bulk RNA‑seq and emerging single‑cell approaches. Researchers can now interrogate how specific lung cell populations respond to pollutants, allergens, or therapeutic compounds with greater statistical power, even when only small tissue samples are available.

Because the protocol relies on reagents commonly found in molecular biology labs, the authors expect rapid adoption across pulmonary research centers. They also suggest that the same principles could be applied to precision‑cut slices from other organs, potentially streamlining gene‑expression studies in heart, liver or kidney tissue. The full method has been made publicly available, paving the way for broader use in drug development and personalized medicine research.