Figure 3.
The Proline Arginine Loop (PAL) family of CNS-tropic capsid variants in cynomolgus macaques emerges after selection with DELIVER.
(A) Amino acid sequence and corresponding peptide sequence logo of the 7-mer insert in the 10 most enriched DNA sequence-level capsid variants in the CNS of two-year-old cynomolgus macaques injected with 3E+13 vg/kg virus library following two rounds of selection with DELIVER. Sequences with the same color are encoded by synonymous DNA codons.
(B) Amino acid sequence and logo of the 7-mer insert in the 10 most enriched amino acid-level capsid variants in the macaque CNS. The rank of each variant corresponds to the sum of the ranks of two synonymous DNA sequences.
(C) Enriched variants contained in the PAL-like cluster generated by k-medoids clustering represented by the medoid sequence PTQGTLR. Individual residues are color-coded according to their functional properties to highlight conserved aspects of the sequence motif. The rank of each variant corresponds to the sum of the ranks of two synonymous DNA sequences.
(D) Predicted structure of the VR-VIII surface loops of AAV9, PAL1A, and PAL-like.1.