The two nucleases ZFN and TALEN each consist of a protein that binds DNA and a protein that can cut DNA. The compound on which these designer nucleases are based is created in advance in a targeted manner using genetic engineering methods.

ZFN and TALEN have been produced since the 1990s. ZFN is produced from a zinc-finger domain and an endonuclease. TALEN results from so-called TALE repeats and also an endonuclease.

ZFN and TALEN are significantly more time-consuming and cost-intensive than the CRISPR/Cas system. In particular, the “programming” of the RNA in the targeted DNA sequence is generally easier and faster to implement. Furthermore, CRISPR/Cas9 may be distinguished from the other two methods because it can accommodate multiple RNAs, which the nuclease can then direct to different DNA sequences. This includes the possibility to edit different sequences of an DNA within the same cell by using CRISPR/Cas9.

Finally, the possibility of modifying genomes without double-strand breaks arises from the possibility of so-called prime editing, which often includes undesirable side effects, especially due to mutations. As a result of the differences between these methods, current research and clinical applications focus on the CRISPR/Cas9 system.