Table 4 Advantage and disadvantage for different strategies

Small molecule activators

(1) Easy to synthesis

(2) Cell permeable and nonimmunogenic

(3) High level of gene editing efficiency

(1) Potential cytotoxicity

(2) Significant background activity

(3) Lack wide-dynamic range

^8,14,18,69

Small molecule inhibitors

(1) Easy to synthesis

(2) Cell permeable and nonimmunogenic

(3) The low level of off-target efficiency

(1) Significant background activity

(2) Lack of easy tunability in clinical application

(3) Difficulties in identification and screening

^{8,14,26,27,69}

Cell-specific promoters

(1) The low level of off-target efficiency

(2) High gene editing specificity in the spatial dimension

(1) Difficulties in screening of more promoter with high cell specificity and high activity

^37,57

Bioresponsive delivery carriers

(1) High capacity

(2) With programmed functionalities

(3) High gene editing specificity in the spatial dimension

(1) Limited by endogenous stimuli

(2) Difficulties in screening of bioresponsive moieties and advanced materials used to synthesize carriers

^{114,119,120,122,126}

Light control

(1) Noninvasiveness

(2) Low toxicity

(3) Reversible property

(4) Easy tunability

(1) Long exposure time

(2) Limited to a narrow spectral range

(3) Strong absorption of light by turbid biological tissues

^{69,126,134,136,137,139,140,141}

Heat control

(1) Noninvasiveness

(2) Easy tunability

(3) High gene editing spatiotemporal specificity

(1) Long exposure time

(2) Low photothermal conversion efficiency

(3) Difficulties in screening of more heat shock promoters

^{18,55,146,147}

Ultrasound control

(1) Noninvasiveness

(2) High transfer efficiency

(3) High gene editing spatiotemporal specificity

(1) Less reversible

(2) Not been fully explored and underutilized

(3) Lack of easy tunability in clinical application

^149,150

Magnetic control

(1) Noninvasiveness

(2) Not disturbed by tissues

(3) Low cytotoxicity

(4) High gene editing spatiotemporal specificity

(1) Not been fully explored and underutilized

(2) Difficulties in screening of magnetic sensing materials

^9,160