A recent publication in Molecular Therapy detailed the data from eight gene therapy clinical trials, including variables such as the AAV serotype employed, the CpG dinucleotide content in the open reading frame of the therapeutic gene, the vector production method, the vector dosage and estimated total capsid dose, the immunosuppressive drugs administered, the correlation of AAV gene transfer with a cytotoxic T lymphocyte response (CTL) response, the outcome peak of the therapeutic transgene, and the durability of the transgene. The power of this clinical trial information is that it is the single largest AAV vector clinical data set for a single disease AAV gene therapy for hemophilia B—and allowed researchers to gain a clear insight into the key determinant for clinical success. Among the variables, CpG content was revealed to be the only factor that correlates well with clinical outcome and long-term transgene expression, with unmethylated CpG content in AAV vectors being the key attribute that triggers transgene expression-limiting immune responses in humans.
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