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. Author manuscript; available in PMC: 2023 Jan 15.
Published in final edited form as: Med. 2022 Nov 22;4(1):31–50.e8. doi: 10.1016/j.medj.2022.11.002

Figure 2.

Figure 2.

Selection with DELIVER yields potent CNS-tropic capsid variants in multiple mouse strains.

(A and B) Amino acid sequence and logo of the 7-mer insert in the 10 most enriched capsid variants with the (A) AQ or (B) DG prefix in the brain of eight-week-old C57BL/6J and BALB/cJ mice injected with 1E+12 vector genomes (vg) virus library following two rounds of selection with DELIVER. Sequences with the same color in each table are encoded by synonymous DNA codons.

(C) Predicted structure of the VR-VIII surface loops of AAV9, MDV1A, and MDV1B.

(D) Fold difference in EGFP mRNA expression from MDV1A compared to AAV9 in the brain and spinal cord of male and female eight-week-old C57BL/6J and BALB/cJ mice injected with 1E+12 vg of MDV1A- or AAV9-CMV-EGFP. Dashed red line represents AAV9-CMV-EGFP expression normalized to 1. Data are represented as mean ± SD (n=3–4); *p<0.05, **p<0.01 (Welch’s t-test between MDV1A- and AAV9-injected mice with Holm-Šídák MCT).

(E) Quantification of transgene delivery efficiency, expressed as vector genomes per diploid genome, of MDV1A- and AAV9-CMV-EGFP in the brain and spinal cord of eight-week-old C57BL/6J and BALB/cJ mice injected with 1E+12 vg of MDV1A- or AAV9-CMV-EGFP. Data are represented as mean ± SD (n=3–4); *p<0.05, **p<0.01 (Welch’s t-test between MDV1A- and AAV9-injected mice with Holm-Šídák MCT).

(F) Representative images of 12 μm mouse brain sagittal cryosections immunostained for EGFP, from eight-week-old C57BL/6J and BALB/cJ mice injected with 5E+11 vg of MDV1A- or AAV9-CMV-EGFP. Insets show detailed features with hematoxylin nuclear counterstain (purple). Black scale bars: 1 mm; white scale bars: 50 μm.

See also Table S1.