What measurement separates cell loss from reversible expression loss?

A decline in circulating protein or functional benefit cannot show whether transduced cells were eliminated, retained vector genomes became transcriptionally quiet, or surviving cells reduced protein output. This distinction affects both safety interpretation and repeat dosing. In a primate muscle study, expression recovered while vector genomes persisted, showing that an apparent durability failure need not mean irreversible loss of transduced cells. A recent pulmonary AAV study measured tissue vector genomes, RNA, protein, and immune responses at 180 days, but a terminal tissue assessment cannot by itself resolve when any divergence began. Which longitudinal measurement would justify the next decision: serial tissue sampling, a validated circulating marker of transduced-cell mass, or paired vector-genome and expression assays despite their sampling burden?