Table 2.

Comparison of viral, non-viral gene delivery, and CRISPR/Cas9 Gene Editing in CAR T-Cell Therapy.

Feature	Viral Gene Delivery	Non-Viral Gene Delivery	CRISPR/Cas9 Gene Editing
Efficiency	High transduction efficiency; stable gene expression.	Lower efficiency; often transient expression.	High editing efficiency; permanent modifications possible.
Cost	Higher due to production complexities and biosafety requirements.	Generally lower, simpler production processes.	Variable; high initial development cost but decreasing as technology matures.
Safety	Risk of insertional mutagenesis and immune response to viral components.	Reduced risk of insertional mutagenesis; lower immunogenicity.	Risk of off-target effects and unintended genetic alterations.
Scale-Up	Scalable but complex due to stringent regulatory requirements.	Easier to scale up and less regulated.	Scalable, but requires precise control and validation of editing tools.
Flexibility and Control	Less control over gene expression post-delivery.	Higher control, including potential for repeat dosing.	High precision in gene modification; allows targeted gene disruptions and insertions.
Technological Maturity	Well-established in clinical settings with approved products.	Emerging technologies, fewer examples of clinical validation.	Rapidly evolving; increasing clinical applications but still less mature than viral methods.
Integration Into Host Genome	Permanent integration possible, leading to long-lasting effects.	Usually no integration, leading to transient effects unless integrating non-viral systems are used.	Targeted integration can be achieved; depends on the CRISPR system and delivery method used.