Figure 5.

Incorporation of Tyrosine Mutants into AAV5 and AAV8 Capsids Does Not Improve Transduction Properties following Intrastriatal Injections

Adult Sprague-Dawley rats received intrastriatal injections of either AAV5 or AAV8 vectors (2 μL of 1.2 × 10¹² vg/μL) as defined in Table 1. One month later, the animals were sacrificed and processed for transgene (GFP) immunoreactivity. (A–D) Representative micrographs of striatal GFP immunoreactivity following injection with AAV5 capsid mutants: (A) T5 WT (n = 9), (B) T5 2Y (n = 8), (C) T5 5Y (n = 8), and (D) T5 1Y (n = 8). (E and F) Stereological cell counts of transduced neurons (E) or transduction volume (F) suggests that incorporation of these mutations does not improve transduction compared with WT AAV5. In contrast, the incorporation of five mutations (T2 5Y) resulted in a dramatic reduction in transduction (*p < 0.0001). (G–J) Representative micrographs of striatal GFP immunoreactivity following transduction with AAV8-based capsids: (G) T8 WT (n = 8), (H) T8 2Y +T (n = 7), (I) T8 1Y (n = 8), and (J) T8 2Y (n = 7). (K and L) As indicated by the stereological quantification (K) and volumetric analysis (L), there were no significant differences between the various mutants except a modest reduction in the number of transduced cells with the T8 2Y virus as compared with T8 2Y +T (**p = 0.02). (E, F, K, and L) Error bars represent the mean + SD.