“…To date, only a few pAgos derived from thermophilic archaea and mesophilic bacteria have been well characterized ( Swarts et al, 2014a , 2015 ; Kaya et al, 2016 ; Zander et al, 2017 ; Cao et al, 2019 ; Chong et al, 2019 ; Hegge et al, 2019 ; Kuzmenko et al, 2019 ; Kim et al, 2020 ; Olina et al, 2020 ; Liu et al, 2021b ). Some Agos can act as programmable endonucleases to cleave targets between nucleotides 10 and 11 using a divalent cation to catalyze the hydrolysis of the phosphodiester bond that lies across nucleotides 10 and 11 of the base-pairing guide ( Swarts et al, 2015 ; Jolly et al, 2020 ; Kuzmenko et al, 2020 ).…”