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. 2023 Apr 19;9(16):eadg6618. doi: 10.1126/sciadv.adg6618

Fig. 1. Identifying engineered AAVs that do not use LY6A for BBB crossing.

Fig. 1.

(A) AAV-PHP.eB can efficiently cross the BBB using membrane-localized LY6A in C57BL/6J mice but not GPI-disrupted LY6A in BALB/cJ mice. (B) Clustering analysis of CNS-tropic engineered AAV insertion sequences. Thickness of connections represents degree of relatedness between nodes. AAVs in yellow show a high degree of relatedness to PHP.eB. AAVs in gray show little relation to PHP.eB or each other. The peptide sequences in two engineered regions (AA587 to AA590 and AA452 to AA458 of the AAV9 capsid for each variant are shown. References: 1: Chan et al. (26), 2: Goertsen et al. (37), 3: Ravindra Kumar et al. (22), 4: Nonnenmacher et al. (24), and 5: Hanlon et al. (20). (C) Surface plasmon resonance (SPR) of engineered AAVs binding to LY6A-Fc captured on a protein A chip. Data are representative of two independent experiments. v.g., viral genome.