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Table 2 Comparison of NK cell engineering reagents

From: Nonviral genome engineering of natural killer cells

Cargo

Efficiency

Viability

Advantages

Disadvantages

Therapeutic uses

Transient mRNA

DNA

Up to 99%

Poor to good

Rapid expression

High efficiency

Transient—no stable genomic integration

Cell viability dependent on cargo (e.g., RNA, DNA)

Transient CAR mRNA

Knockout of genes that suppress or inhibit NK cell function

Knock-in of activating receptors or genes that promote NK cell function

Transposon

Up to 80%

Poor to good

Cost effective

Large cargo capacity

Stable integration

Potential insertional mutagenesis

Transposon must be delivered as DNA

Large cargo delivery (e.g., CAR in combination with activating receptors or cytokines)

Cas9

Base editor

Prime editor

Up to 100%

Poor to excellent

High precision

High efficiency

Large-scale insertion or deletion

Potential off target editing

Indels and translocations

Knockout genes that suppress or inhibit NK cell function

Knock-in of activating receptors or genes that promote NK cell function

Treating patients bearing disease caused by a single base pair mutation