Transduction profiles in minipig following MRI guided delivery of AAV-5 into thalamic and corona radiata areas

As a step towards clinical use of AAV-mediated gene therapy, brains of large animals are used to settle delivery parameters as most brain connections, and relative sizes in large animals and primates, are reasonably common. Prior to application in the clinic, approaches that have shown to be successful in rodent models are tested in larger animal species, such as dogs, non-human primates, and in this case, minipigs. We evaluated alternate delivery routes to target the basal ganglia by injections into the more superficial corona radiata, and, deeper into the brain, the thalamus. Anatomically known connections can be used to predict the expression of the transgene following infusion of AAV5. For optimal control over delivery of the vector with regards to anatomical location in the brain and spread in the tissue, we have used magnetic resonance image-guided convection-enhanced diffusion delivery. While the transduction of the cortex was observed, only partial transduction of the basal ganglia was achieved via the corona radiata. Thalamic administration, on the other hand, resulted in widespread transduction from the midbrain to the frontal cortex Compared to other methods, such as delivery directly to the striatum, thalamic injection may provide an alternative when for instance, injection into the basal ganglia directly is not feasible. The study results suggest that thalamic administration of AAV5 has significant potential for indications where the transduction of specific areas of the brain is required. •The minipig brain was used to model AAV delivery to the CNS.•Both superficial and deep areas can targeted by MRI guided infusion.•Anterograde and retrograde transduction patterns observed.•With thalamic delivery a broad range of transduction can be achieved in areas away from the injection site.