Table 2.

Comparison between genetic modification using lentiviral or retroviral vectors and gene editing.

Retroviral/lentiviral vectors		Gene editing
Advantages	Disadvantages	Advantages	Disadvantages
High transduction efficiency and easy transduction procedures	Random integration into the genome	Endogenous regulation of transgenic TCRs/CARs. In CARs-T cells, endogenous regulation avoids overexpression, tonic signaling and T-cell exhaustion	Lower modification efficiency
Easy manufacturing on small scale	Variable transgene expression	Homogeneous expression	Off-target double-stranded breaks
	Artificial regulation from viral vector promoter can lead to transgene silencing or overexpression	Knock-in and knock-out can be multiplexed. Potential to increase T cell potency and generate off-the-shelf T-cell products	Electroporation, Cas9, and HDR donor-induced toxicity. Decreased T-cell expansion
	Costly and time-consuming large-scale manufacturing at GMP/clinical grade	Viral and non-viral methods. The non-viral methods allow for fast reagent manufacturing at GMP/clinical level
		No TCR mispairing
		Lower cost with non-viral methods

CAR, chimeric antigen receptor; GMP, good manufacturing practices; HDR, homology-directed repair; TCR, T-cell receptor.