Prediction of Adeno-Associated Virus Neutralizing Antibody Activity for Clinical Application

摘要: Patients with neutralizing antibodies (Nabs) against adeno-associated virus (AAV) are usually excluded from the treatment AAV vectors. To develop a standard assay for detecting Nab inhibition activity, we systematically studied current assays in vitro and vivo. Several factors were found that influence titers based on assay, including sera volume, dose per cell, cell number choice of transgenes. When titer was performed vivo via intramuscular (IM) or systemic administration, fourfold increase sensitivity measurement observed compared an identical test. better mimic clinical setting, after passively transferring human Nabs into mice, blood collected before injection vector used analysis IM injection. The results showed delivered had similar pattern to administration. These studies indicate critical parameters necessary optimizing is more sensitive than inclusion/exclusion criteria. variables identified by this study may explain some compounding data seen date respect efficiency transduction various phase I trials.