I'm confused because Crispr-Cas9 system can lead to significant on-target mutagenesis, such as frequent large-fragement deletions (kilobase scale).
do you want to deactivate a target domain function with maintaining other domain functions of a gene?
1. deletion can change the shape of the protein with a high probability
2. Substitution is likely to alter the function of the target domain of the protein and leave the function of other domains unchanged.
If you want deletions, you can't just use cas9 to randomly act and achieve the desired deletions.
If you want substitution, you can use Cas9 and donor DNA together to change the target domain as desired. Alternatively, you can change the desired residue with a low confidence if you use the deaminase-fused-Cas9.
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