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Mol Ther Methods Clin Dev DOI:10.1016/j.omtm.2018.07.006

Efficient Gene Transfer to the Central Nervous System by Single-Stranded Anc80L65.

Publication TypeJournal Article
Year of Publication2018
AuthorsHudry, E, Andres-Mateos, E, Lerner, EP, Volak, A, Cohen, O, Hyman, BT, Maguire, CA, Vandenberghe, LH
JournalMol Ther Methods Clin Dev
Date Published2018 Sep 21

Adeno-associated viral vectors (AAVs) have demonstrated potential in applications for neurologic disorders, and the discovery that some AAVs can cross the blood-brain barrier (BBB) after intravenous injection has further expanded these opportunities for non-invasive brain delivery. Anc80L65, a novel AAV capsid designed from reconstruction of the viral evolutionary lineage, has previously demonstrated robust transduction capabilities after local delivery in various tissues such as liver, retina, or cochlea, compared with conventional AAVs. Here, we compared the transduction efficacy of Anc80L65 with conventional AAV9 in the CNS after intravenous, intracerebroventricular (i.c.v.), or intraparenchymal injections. Anc80L65 was more potent at targeting the brain and spinal cord after intravenous injection than AAV9, and mostly transduced astrocytes and a wide range of neuronal subpopulations. Although the efficacy of Anc80L65 and AAV9 is similar after direct intraparenchymal injection in the striatum, Anc80L65's diffusion throughout the CNS was more extensive than AAV9 after i.c.v. infusion, leading to widespread expression in the cerebellum. These findings demonstrate that Anc80L65 is a highly efficient gene transfer vector for the murine CNS. Systemic injection of Anc80L65 leads to notable expression in the CNS that does not rely on a self-complementary genome. These data warrant further testing in larger animal models.


Alternate JournalMol Ther Methods Clin Dev
PubMed ID30109242
PubMed Central IDPMC6083902
Grant ListK99 AG047336 / AG / NIA NIH HHS / United States
P30 EY003790 / EY / NEI NIH HHS / United States