Table 3 Comparison of systemic delivery methods

AMOs

Complementary to mature miRNAs

AMOs are widely used to inhibit miRNAs in vitro and in vivo.

Modified AMOs

-OMe

2′-O-methyl modification

Modified AMOs have more stability and efficiency than AMOs.

-MOE

2′-O-methoxyethyl modification

Especially LNA increases the stability, efficiency and specificity.

-LNA

2′,4′-methylene modification

Sponges

Competitive inhibitors which are transcripts expressed from plasmid with strong promoters, containing multiple, tandem binding sites to the miRNAs of interest.

Sponges can block a whole family of related miRNAs. Selectable marker or reporter gene in the vector allows to isolate a fraction of cells in which the family of miRNAs is strongly inhibited.

AAV

Adenovirus- associated vectors

AAV are also widely used for systemic delivery. While the toxicity of viral mediated delivery is rarely reported, it remains controversial.

(PEI/miR complex)

(Intratumoral injection)

PEI/miR complex, plasmid and CC9 are probably useful for delivery. However we cannot assure their utility because few experiments using them for delivery have been performed.

Plasmid

miRNA-expressing plasmids encapsulated in small multilamellar cationic liposome (DOTAP/cholesterol)

CC9

A specific tumor-homing and -penetrating bifunctional peptide conjugated with oligonucleotides.