David R. Liu, wei Hsi Yeh
The disclosure provides adenosine deaminases that are capable of deaminating adenosine in DNA to treat cancers, such as melanoma and glioblastoma. The disclosure also provides fusion proteins, guide RNAs and compositions comprising a Cas9 (e.g., a Cas9 nickase) domain and adenosine deaminases that deaminate adenosine in DNA, for example in a STAT3 gene. In some embodiments, adenosine deaminases provided herein are used to modify the STAT3 gene so that its protein product, STAT3, is unable to be activated. In some embodiments, the methods and compositions provided herein are used to treat melanoma or glioblastoma.