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. Author manuscript; available in PMC: 2020 Nov 9.
Published in final edited form as: ACS Nano. 2019 Oct 7;13(10):10961–10971. doi: 10.1021/acsnano.9b01515

Figure 1.

Figure 1.

Elucidation of targeted ANS-to-CNS uptake ligands (TACL) that enrich bacteriophage accumulation in the CNS after uptake into the autonomic nervous system. After three rounds of an in vivo screen, bacteriophage isolated from heart, brain, and spinal cord were analyzed by NGS to deduce tissue enrichment of a consensus domain (A). While an initial 50:50 mix of circular (C7C) and linear (Ph.D.12) phage was injected, only 2% of phage-sequences in the final CNS lysate were derived from a C7C background, yet both phage-populations yielded 84% and 66% CNS accumulation versus heart tissue (15% and 34%, respectively) (B). Based on NGS data, phage candidates for TACL peptides sequences were identified with ≥10-fold targeted enrichment in either heart (H; red), brain (B; yellow), spinal cord (S; blue) (C). Five bacteriophage clones showed enrichment in brain and spinal cord tissue after IP injection (D).