AAV-PHP.B Administration Results in a Differential Pattern of CNS Biodistribution in Non-human Primates Compared with Mice

William A. Liguore, Jacqueline S. Domire, Dana Button, Yun Wang, Brett D. Dufour, Sathya Srinivasan, Jodi McBride

    Research output: Contribution to journalArticle

    2 Scopus citations


    The ability of recombinant adeno-associated virus (AAV) to deliver transgenes to the CNS has allowed for several advancements in the field of gene therapy to treat brain disorders. Although most AAVs do not readily cross the blood-brain barrier and transduce the CNS following peripheral administration, AAV-PHP.B has recently been shown to transduce brains of mice with higher efficiency compared with its parent serotype, AAV9, following injection into the retro-orbital sinus. Here, we extended this foundational work by comparing AAV-PHP.B transduction efficiency in wild-type C57BL/6J mice using four clinically applicable delivery strategies including two intravascular (intra-jugular vein and intra-carotid artery) and two intra-cerebral spinal fluid (CSF) routes (intra-cisterna magna and intra-lateral ventricle). We scaled up these comparisons in a larger-animal model and evaluated transduction efficiency of AAV-PHP.B in the rhesus macaque. We found widespread and largely equal CNS transduction in mice following all four injection strategies, whereas we observed a differential pattern of transduction in macaques with broad cortical and spinal cord transduction seen after intrathecal administration and only very low transduction following intravascular administration. Taken together, these results suggest that AAV-PHP.B may be a useful gene therapy vector for neurological disorders, particularly those stemming from broad cortical or spinal cord neuropathology. Liguore and colleagues characterize biodistribution of AAV-PHP.B in the rodent and rhesus macaque CNS following intra-CSF and intravascular delivery modalities. Although equal transduction efficiency was seen in mice regardless of delivery route, intra-cisterna magna infusion led to superior transduction efficiency compared with intra-carotid artery infusion in the rhesus macaque CNS.

    Original languageEnglish (US)
    JournalMolecular Therapy
    StateAccepted/In press - Jan 1 2019



    • AAV-PHP.B
    • AAV9
    • adeno-associated virus
    • brain
    • CNS
    • gene therapy
    • gene transfer
    • mouse
    • rhesus macaque
    • viral transduction

    ASJC Scopus subject areas

    • Molecular Medicine
    • Molecular Biology
    • Genetics
    • Pharmacology
    • Drug Discovery

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