Comment on: “First-in-human trial of Dz13 for nodular basal-cell carcinoma”.

Nucleic-acid-based drugs1 are a novel class of drugs with great therapeutic potential. Among these are DNAzymes, which contain short stretches of single-stranded DNA molecules synthesised in vitro. A DNAzyme can recognize through Watson-Crick basepairing a specific messenger RNA (mRNA) sequence and induce cleavage between a purine and a pyrimidine residue. Upon cleavage, the target mRNA undergoes accelerated degradation, which leads to a reduction in the concentration of the encoded protein and its related biological functions. Thus, DNAzymes can potentially be used to target specific mRNA in diseases dependent on individual genes. Nevertheless, although the great therapeutic potential of these drugs has been noted in preclinical studies, data about their use in human beings are missing. In The Lancet, Eun-Ae Cho and colleagues report a first-in-human study of the DNAzyme Dz13 in patients with nodular basal-cell carcinoma. The therapeutic promise of Dz13 is strongly supported by previous animal studies. The drug targets the mRNA of the JUN proto-oncogene: this target is particularly well suited for the purpose of the study, as c-Jun protein is minimally expressed in normal skin tissue but concentrations are notably increased in skin cancer tumours. Additionally, the model tumour pathology chosen is well suited for clinical investigation because basal-cell carcinomas are easily accessible, monitoring is straightforward, the risk of systemic tumour spread is low, and the therapeutic drug can be injected locally.