Adeno-Associated Viral (AAV) vectors packaging the CRISPR/Cas9 system (AAVCRISPR) can efficiently modify disease-relevant genes in somatic tissues with high efficiency. AAV vectors are a preferred delivery vehicle for tissue-directed gene therapy because of their ability to achieve sustained expression from largely non-integrating episomal genomes. However, for genome editing applications, permanent expression of non-human proteins such as the bacterially-derived Cas9 nuclease is undesirable. Recent studies indicate a high prevalence of neutralizing antibodies and T-cells specific to the commonly used Cas9 orthologs from Streptococcus pyogenes (SpCas9) and Staphylococcus aureus (SaCas9) in humans. Additionally, persistent expression of CRISPR/Cas9 has the potential to increase the chances of off-target cutting. There is a need for efficient genome editing in vivo, with controlled transient expression of CRISPR/Cas9. The topic of my thesis covers the development of a self-deleting AAVCRISPR system that introduces insertion and deletion mutations into AAV episomes, understanding the effects AAV-CRISPR editing in vivo in a Cas9 immunized mouse model, and the characterization of AAV integrations into the genome in the context of CRISPR-based gene editing.