Table 1.

Pros and Cons analysis of the delivery methods. na: not applicable

System	Pros	Cons	Packaging Size	Immunogenicity	Insertional Mutagenesis	Tissue/Cell Tropism	Ref.
AVs	High packing capacity	High immunogenic response	> 8 Kb	High	No	Yes	[14–20]
AAVs	Low immunogenic response, small viral particle size	Low packing capacity	⁓4.5 Kb	Tissue dependent	No	Yes	[14–20]
γ-Retroviruses	High packing capacity	Only dividing cells can be infected, genome integration of target sequence and high risk of oncogenic mutations	< 8 Kb	Moderate	Yes	Yes	[21]
LVs	Low immunogenic response	Genome integration of target sequence and high risk of oncogenic mutations	< 8 Kb	Low	Yes	No	[22–26]
RNPs	Low immunogenic response	Cells cannot be selected with antibiotics or fluorescent markers	na	Low	No	No	[27–36]
CPPs	No transfection reagents need to be used	Cas9 needs to be chemically conjugated to CPPs	na	CPP dependent	No	No	[37–40]
Exosomes	Low immunogenic response, Self-accumulating in tumor mass	Low efficiency of encapsulation, easily degraded	Exosome size dependent	Low	No	Yes	[41–47]
Nanoparticles	Can be conjugated with chemical or physical compounds	Difficult to use	na	Nanoparticle dependent	No	Nanoparticle dependent	[48–53]
Nanoclews	Release dependent on the microenvironment conditions	High immunogenic response	na	High	No	Nanoclew dependent	[54, 55]
IDLVs	Reduced risk of insertional oncogenic mutations	Genome integration of target sequence in non-dividing cells	< 8 Kb	Low	Only in non-dividing cells	No	[70]