Key result
Brain accumulation of the PHP.eB capsid exceeded that of AAV9, with a nearly 20-fold greater affinity for brain endothelial receptors, demonstrating the utility of PET imaging for tracking viral vectors.
A novel PET imaging technique using Cu-64 labeled multichelator constructs can successfully track AAV capsid brain accumulation in vivo, informing future capsid design.
PET enables AAV capsid tracking in animal models; leaves open clinical translation for vector design.
Adeno-associated viruses (AAVs) are typically single-stranded deoxyribonucleic acid (ssDNA) encapsulated within 25-nm protein capsids. Recently, tissue-specific AAV capsids (e.g. PHP.eB) have been shown to enhance brain delivery in rodents via the LY6A receptor on brain endothelial cells. Here, we create a non-invasive positron emission tomography (PET) methodology to track viruses. To provide the sensitivity required to track AAVs injected at picomolar levels, a unique multichelator construct labeled with a positron emitter (Cu-64, t1/2 = 12.7 h) is coupled to the viral capsid. We find that brain accumulation of the PHP.eB capsid 1) exceeds that reported in any previous PET study of brain uptake of targeted therapies and 2) is correlated with optical reporter gene transduction of the brain. The PHP.eB capsid brain endothelial receptor affinity is nearly 20-fold greater than that of AAV9. The results suggest that novel PET imaging techniques can be applied to inform and optimize capsid design.
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Seo et al. (2020) studied this question. 64Cu-labeled AAV-PHP.eB vs. 64Cu-labeled AAV9 or AAV9-TC was evaluated on Brain accumulation of AAV capsids. Brain accumulation of the PHP.eB capsid exceeded that of AAV9, with a nearly 20-fold greater affinity for brain endothelial receptors, demonstrating the utility of PET imaging for tracking viral vectors.
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