AAV dose conversion is not a single mathematical formula, but a structured scientific argument that combines administration route, target organ size, species transduction efficiency, immunobiology and product quality. Simply equating mouse vg/kg directly to human vg/kg is a common mistake because target organ/cell numbers are not proportional to body weight, and there are species differences in AAV receptor biology and glycan presentation [12-41].
Conversion path one: body weight conversion (vg/kg), suitable for systemic/intravenous administration. In clinical IV administration, administration is usually based on body weight (vg/kg = total vg/kg body weight). The AAV field linearly converts based on body weight and does not use body surface area (BSA) - this is a key difference from traditional small molecule/antibody drugs. Basis: AAV liver/heart/myocardial transduction is reported in vg/kg in large animals, and the SMA clinical Zolgensma dose of 1.1×10^14 vg/kg is directly extrapolated from NHP vg/kg data [12-11,12-41].
Conversion path two: organ weight/volume conversion, suitable for local/intra-organ injection. When injecting into an organ with clear structural boundaries, it is converted based on organ weight or volume. Clinical local injection is usually based on a fixed dose (vg/subject) or a fixed concentration (vg/mL/subject). Examples of eye vitreous volume conversion: mouse 0.0044 mL, dog 3 mL, NHP 2 mL, human 4 mL [12-44].
Conversion path three: Allometric Scaling, for auxiliary reference only. The classic formula Y=aW^b is based on body surface area normalization and is only a supportive reference for AAV and cannot replace species-specific biodistribution, efficacy, toxicology and potency data [12-42].
Conversion path four: Activity Factor corrects cross-species transduction efficiency. The composite metric represents expected interspecies differences in transduction and transgene expression between animal models and humans. Example: scAAV2/8-LP1-hFIXco mice → NHP peak FIX levels decreased 20-fold, NHP → humans decreased 3-fold; Valoctocogene roxaparvovec (AAV5) NHP to human dose-adjusted peak ratio was 0.38 [12-43].
The conversion difference between systemic IV vs local/organ injection: System IV is linearly converted according to vg/kg; local injection is converted according to organ volume/fixed dose, and linear scaling of body weight is not applicable. Extrapolation between species needs to be corrected: capsid receptor differences (AAV-PHP.B/Ly6a is only effective for C57BL/6J), pre-existing neutralizing antibodies (NHP/human prevalence is high), opposite liver zone distribution (mouse periportal vs NHP pericentral), high-dose toxicity threshold NHP/pig is more sensitive than mice (mice tolerate >1×10^14 vg/kg, NHP is about 2×10^14 GC/kg means severe toxicity) [12-7,12-11,12-12,12-15]. Mice → NHP experience conversion: mice commonly use 1×10^12 vg/20 g = 5×10^13 vg/kg, NHP equivalent starts at 2×10^12 vg/kg and then ramps up according to effect/toxicity [12-11].
Conversion precautions: The titer determination method, empty/solid shell ratio, potency determination and vector preparation comparability must be verified before using the literature dose; scAAV and ssAAV cannot use universal potency multipliers, and data need to be directly compared; large differences in dosage between newborn animals and adult animals need to be reported separately; FDA/EMA do not provide fixed conversion formulas and require scientific demonstration based on product specificity. High-dose system AAV must have NHP or large animal biodistribution and toxicology data [12-41,12-43].