Table 1.

Overview of available approaches to overcome precision, off-target (OT) and targetability issues.

Goal	Type	Editor	Efficiency*	Editing window (vs 3–10*)	Off-targets*	References
Precision	Deaminase mutations	ABE9e-NG (R111T, N127K, Q154R) ABE8e-N108Q ABE9 (N108Q, L145T)	Similar Similar  > -20%	(3)4–7(8) at similar activity 4–7 5–6	Reduced DNA and RNA OTs	32 24
	Split editor	PIGS-ABE8e sABE v3.22	> -40%  > -25%	4–9 4–7	Reduced DNA and RNA OTs	37 38
	Effector domain	ABE8e-e18	> -10%	5–7	Reduced DNA OTs	40
Off-target reduction	Deaminase mutations	ABE8e-V106W ABE8.17-m-V106W ABE8e-WA ABE8e-WQ	Similar  > -10% Similar  > -20%	Similar Similar 4–8 4–8	Reduction of DNA & RNA OTs Reduced RNA OTs	23 18 33
	Deaminase mutation (+ Cas9 variant)	SpRY-ABE8e-F148A CE-ABE8e-SpRY CE-ABE8e-dV-SpRY	Similar Similar Similar	Similar Similar Similar	Reduced RNA OTs Slightly reduced DNA OTs and reduced RNA OTs Reduced indels, RNA and DNA OTs	36 34 35
	Cas9 variant	Sniper2L	Low mismatch tolerance (only 1 tolerated)			39
Target-ability	Cas9 variant	ABEmax-SpRY ABE8e-SpRYc	PAMless; targetability across NNN PAMs but likely massive increase in DNA OTs PAMless; at certain selected loci more unbiased than ABE8e-SpRY			25 47

*Mostly compared to ABE8e.