Ian Boylan

The APOBEC family of deaminase proteins has one of the most prevalent mutation signatures in several forms of cancer that consists of a C to U base-modification. Within the APOBEC3 family, APOBEC3B (A3B) has been shown to be upregulated in many different cancers, and in particular, bladder, head/neck, lung, and cervical cancer. Deamination activity is controlled by the protein’s catalytic site that is coordinated by a central zinc atom. While a significant amount of research has been conducted on understanding this catalytic activity and the motifs that it targets, efforts to disrupt this activity have been largely unsuccessful. Nanobodies obtained from alpacas were evaluated for the binding affinity and effect on A3B’s catalytic activity. In contrast to antibodies, nanobodies are attractive due to their small size, versatile binding, and stability. Two separate nanobodies, B1 and G8, were able to successfully disrupt catalytic activity through binding and are considered the first, non-viral biological inhibitors of A3B. By preventing deamination activity, it therefore can inhibit cancer mutagenesis. With A3B’s upregulation in several forms of cancer, binding of the B1 and G8 nanobodies can potentially lead to the development of therapeutic methods, especially since A3B is considered a nonessential enzyme. While more research is needed before considering therapeutic options, the interaction between protein and nanobody may prove useful in disrupting and knockdown of A3B’s potent catalytic activity.