Table 2. Comparison between ZFNs, TALENs, and CRRISR/Cas systems for genome editing.

	ZFNs	TALENs	CRISPR/Cas
Target DNA recognition	Protein–DNA	Protein–DNA	RNA–DNA
Key components	ZF-Fok I fusion protein	TALE-Fok I fusion protein	Guide RNA and Cas9 protein
Function mode	ZF proteins recognize target DNA sequences → dimerization of Fok I nucleases induces DSBs of DNA → DSBs are repaired by NHEJ or HDR	TALE proteins recognize target DNA sequences → dimerization of Fok I nucleases induces DSBs of DNA → BSDs are repaired by NHEJ or HDR	Guide RNA recognizes target DNA sequence next to a NGG motif → Cas9 induces DSBs of DNA → DSBs are repaired by NHEJ or HDR
Advantages	Highly efficient and specific	Highly efficient and specific	Highly efficient, easy to be constructed, and capable of editing multiple sites simultaneously
Disadvantages	Large-scale screening, time-consuming and expensive to be constructed	Tedious and time-consuming to be constructed	PAM motif next to target sequence required

DSB, double strand break; NHEJ, non-homologous end joining; HDR, homology-directed repair.