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The Neurotropic Properties of AAV-PHP.B Are Limited to C57BL/6J Mice.

ABSTRACT: Improved delivery of adeno-associated virus (AAV) vectors to the CNS will greatly enhance their clinical utility. Selection of AAV9 variants in a mouse model led to the isolation of a capsid called PHP.B, which resulted in remarkable transduction of the CNS following intravenous infusion. However, we now show here that this enhanced CNS tropism is restricted to the model in which it was selected, i.e., a Cre transgenic mouse in a C57BL/6J background, and was not found in nonhuman primates or the other commonly used mouse strain BALB/cJ. We also report the potential for serious acute toxicity in NHP after systemic administration of high dose of AAV.

SUBMITTER: Hordeaux J

PROVIDER: S-EPMC5911151 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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The Neurotropic Properties of AAV-PHP.B Are Limited to C57BL/6J Mice.

Hordeaux Juliette J Wang Qiang Q Katz Nathan N Buza Elizabeth L EL Bell Peter P Wilson James M JM

Molecular therapy : the journal of the American Society of Gene Therapy 20180202 3

Improved delivery of adeno-associated virus (AAV) vectors to the CNS will greatly enhance their clinical utility. Selection of AAV9 variants in a mouse model led to the isolation of a capsid called PHP.B, which resulted in remarkable transduction of the CNS following intravenous infusion. However, we now show here that this enhanced CNS tropism is restricted to the model in which it was selected, i.e., a Cre transgenic mouse in a C57BL/6J background, and was not found in nonhuman primates or the ...[more]

PMID: 29428298

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