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Table 1 Pros and Cons analysis of the delivery methods. na: not applicable

From: Delivery systems of CRISPR/Cas9-based cancer gene therapy

System Pros Cons Packaging
Size
Immunogenicity Insertional Mutagenesis Tissue/Cell Tropism Ref.
AVs High packing capacity High immunogenic response > 8 Kb High No Yes [14,15,16,17,18,19,20]
AAVs Low immunogenic response, small viral particle size Low packing capacity ⁓4.5 Kb Tissue dependent No Yes [14,15,16,17,18,19,20]
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 [22,23,24,25,26]
RNPs Low
immunogenic response
Cells cannot be selected with antibiotics or fluorescent markers na Low No No [27,28,29,30,31,32,33,34,35,36]
CPPs No transfection reagents need to be used Cas9 needs to be chemically conjugated to CPPs na CPP dependent No No [37,38,39,40]
Exosomes Low
immunogenic response, Self-accumulating in tumor mass
Low
efficiency of encapsulation, easily degraded
Exosome size dependent Low No Yes [41,42,43,44,45,46,47]
Nanoparticles Can be conjugated with chemical or physical compounds Difficult to use na Nanoparticle dependent No Nanoparticle dependent [48,49,50,51,52,53]
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]