Table 4.

Advantages and disadvantages of each delivery method of siRNA.

Method of delivery	Advantages	Disadvantages
Intra-cerebroventricular	Directly in the brain; Distribute in all brain	Difficult to apply in clinic; Dilution of the siRNA and potential degradation; Off target effects on other brain regions
Intra-vascular, tail vein and carotid	Possible in clinic	Difficulties to cross BBB; Off target effects on other organs (i.e., Liver); Dilution of the siRNA; Increase chance of siRNA degradation
In the brain structures: Cortex and hippocampus	In the targeted brain region; Small amount of siRNA	Difficult to apply in clinic; Mechanical lesion by the injection; Neuroinflammation
Intra-nasal	Target the brain; Diffusion along the perivascular space; Possible in clinic; Accommodate large molecules	Potential dilution of siRNA and degradation; Off target effects on lungs and other brain regions