Impact of unit notations on quantitative biodistribution analysis of adeno-associated virus vectors-based gene therapy products

In gene therapy involving the use of adeno-associated virus (AAV) vectors, the biodistribution of vector genome has been expressed in units of "copies/μg genomic DNA (gDNA)." However, gDNA content vary across tissues, thus affecting the biodistribution results between tissues reported in copies/μg gDNA. Therefore, we evaluated vector genome biodistributions following intra-cisterna magna injection of AAV1, AAV5, and AAV9 in cynomolgus monkeys using concentration units (copies/g tissue or mL blood), which are commonly used in conventional pharmacokinetic evaluations. We compared these results with values expressed in copies/μg gDNA. Correlations between the concentration units and copies/μg gDNA varied across sample types (including blood, central nervous tissues, and peripheral tissues) and within central nervous and peripheral tissues. Evaluating tissue concentrations relative to blood concentrations revealed that concentration units provided clearer insights into brain distribution mechanisms and peripheral tissue exposure. These findings provide valuable insights for biodistribution studies focused on mass balance and quantitative pharmacokinetic analyses, potentially accelerating advancements in gene therapy utilizing AAV vectors.