The success of adeno-associated viral (AAV) vectors for gene replacement applications has spurred interest to repurpose AAV into a platform for CRISPR/Cas9 gene editing. Yet, AAV vector behaviors that are critical for gene editing have been unexplored. To safely and effectively combine AAV and CRISPR/Cas9 for in vivo applications, a better understanding of the potential sites for gene editing and the possible editing outcomes at those sites is critical. Historically, AAV vectors have been used for their ability to generate sustained transgene expression. The potential for low or transient expression of AAV- delivered transgenes has been unexamined. This creates a blind spot for AAV-based genome editing applications because only minimal transgene expression is required for activity. To address this problem, we develop a novel AAV tropism screening method that captures low and transient expression and radically redefines the extent of in vivo AAV gene transfer following systemic delivery. With further refinement of this method, we are also able to distinguish cells with transient transduction by AAV. In addition to uncovering the potential sites for editing, predicting editing outcomes is also key. CRISPR/Cas9 deletion strategies can generate heterogenous mutations in the targeted gene alleles, but the degree to which this impacts in vivo AAV-CRISPR/Cas9 deletions is unknown. Here, we develop a system to characterize in vivo allelic heterogeneity in single cells following AAV-CRISPR/Cas9. We find that allelic heterogeneity is unexpectedly high in transduced tissues following AAV-CRISPR/Cas9 and that the driver of this heterogeneity is not incomplete editing but rather undesired editing. Lastly, developing methods to test the in vivo activity of newly developed gene editing technologies will speed their application to the clinic. Here, we validate a system to visualize prime editing in mammalian cells and demonstrate that prime editing can be achieved with a split AAV vector construction. In summary, reengineering AAV vectors into a gene editing platform requires a stronger understanding of vector biodistribution and in vivo gene editing outcomes. The work presented in this thesis advances our knowledge in both of these areas and will hopefully accelerate the development of new clinical tools.