Table 2.

Reviewing recent studies utilizing EVs loaded with therapeutic cargo.

Engineered EV Cargo	Example:	EV Cell Source:	Major Findings:	Reference:
Cargo: siRNA	PTEN-siRNA	BM-MSCs	When administered intranasally to rat models of spinal cord injury, MSC-EVs loaded with PTEN-siRNA via simple incubation silenced PTEN expression in spinal cord lesions, regenerated corticospinal axons, and resulted in significant functional and structural recovery.	(S. Guo et al., 2019)
Cargo: siRNA	lincRNA-Cox2-siRNA	Mouse primary astrocytes	In vivo: Intranasally delivered lincRNA-Cox2-siRNA loaded EVs could reach the brain and reduce LPS-induced microglial proliferation	(Liao et al., 2020)
Cargo: siRNA	LincRNA-Cox2-siRNA	Mouse primary astrocytes	In vivo: EVs via intranasal administration containing lincRNA-Cox2 siRNA were able to restore microglial phagocytic activity in mice administered with morphine.	(Hu et al., 2018)
Cargo: hsiRNA	HsiRNA targeting Huntingtin mRNA	Human primary U87 glioblastoma cells	In vitro: hsiRNA-loaded EVs were taken up by mouse primary cortical neurons and silenced Huntingtin (Htt) mRNA and HTT protein expression. In vivo: EVs induced bilateral Htt mRNA silencing after a unilateral stereotactic injection into striata of the mouse brain. This suggests that the EVs can travel and unload gene-regulating cargo efficiently.	(Didiot etal., 2016)
Cargo: Protein	Prostaglandin receptor antagonist	Human BM-MSCs	In vivo: EVs suppressed inflammatory cytokines, exhibited sustained inhibition of reactive astrocytes, and rescued the memory and learning deficiencies induced by hippocampal damage in mice.	(S. Y. Chen et al., 2019)