Positron emission tomography imaging of novel AAV capsids maps rapid brain accumulation. Academic Article uri icon


  • 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=12.7h) 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.

published proceedings

  • Nat Commun

altmetric score

  • 11.55

author list (cited authors)

  • Seo, J. W., Ingham, E. S., Mahakian, L., Tumbale, S., Wu, B. o., Aghevlian, S., ... Ferrara, K. W.

citation count

  • 14

complete list of authors

  • Seo, Jai Woong||Ingham, Elizabeth S||Mahakian, Lisa||Tumbale, Spencer||Wu, Bo||Aghevlian, Sadaf||Shams, Shahin||Baikoghli, Mo||Jain, Poorva||Ding, Xiaozhe||Goeden, Nick||Dobreva, Tatyana||Flytzanis, Nicholas C||Chavez, Michael||Singhal, Kratika||Leib, Ryan||James, Michelle L||Segal, David J||Cheng, R Holland||Silva, Eduardo A||Gradinaru, Viviana||Ferrara, Katherine W

publication date

  • January 2020