There have been massive advances in the development of biotherapeutics but progress has been slow in targeting intracellular processes due in part to the difficulty of measuring cell penetration and distribution between intracellular compartments and organelles. A research group based at Tufts University, USA, has developed a novel assay, the Chloroalkane Penetration Assay (CAPA), as a powerful tool to meet this challenge. They have shown how CAPA can help in following the modulation of biomolecule cell penetration, including structure-penetration profiling of bioactive stapled peptides and peptides fused to cell-penetrating sequences, measuring the effect of environmental factors on penetration, and tracing the movement of potential biotherapeutics between organelles.