“The best trade-off one can currently imagine is to engineer rAAV vectors with better transduction efficiency, carrying optimized therapeutic transgenes and with reduced immunogenic profiles (CpG depleted genome, [Faust et al.], inert capsids, contaminant-free batches, minimum amounts of empty capsids, etc.). Such vectors would provide a higher therapeutic index, as they would permit therapeutic efficiency at doses sufficient to bypass pre-existing humoral immunity, but not high enough to trigger deleterious cellular immunity.”
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