Fig. 5: Intranasal adeno-associated virus delivery of co-packaged Cas9 DNA and a HTR2A-targeting guide RNA improves memory in aged mice.

A Aged male C57Bl6 mice were treated intranasally with vehicle or with 2.0 × 10¹¹ viral particles on day 1, and 5-weeks later tested behaviorally using a spontaneously alteration memory test. Mice treated with AAV9-CRISPR/Cas9 showed a significant increase in the percent spontaneous alterations (p-value = 0.0007, N = 15 mice per group, asterisk, blue bar). B Representative, merged immunofluorescence image of vehicle-control animals depicting the presence of 5HT-2A receptor protein labeling in apical dendrites in the CA2/CA3 region of the hippocampus. The blue staining reflects nuclear staining with DAPI. As expected, there was no expression of GFP in vehicle controls. C Identical to Panel B with the exception that the merged image is from a AAV9-CRISPR/Cas9-treated mouse brain. In this case, strong GFP labeling was observed in cell bodies while there was an observed decrease in 5HT-2A receptor fluorescence. Images are representative of 3 separate mice for each group.