Chronopharmacology of AAV gene therapy in mice

The promise of adeno-associated virus (AAV) vectors for gene therapy is held back by the cost and toxicity of the large doses required. This experiment explored the chronopharmacology of AAVs in mice by studying how circadian phase at the time of injection impacted AAV efficacy and revealed that intraperitoneal doses of AAVs injected during the resting phase (ZT6, 12:00PM) produced greater transgene expression over several weeks than equivalent doses injected during the waking phase (ZT18, 12:00AM). This insight could lead to future work that improves safety and reduces costs of AAV gene therapy and other nanoparticle therapies.