Table 1.

Summary of properties of three generations of antisense oligonucleotides in comparison with phosphodiesters.

ASOs	Ability to Penetrate Cells	Stability in Vivo	Binding to Target mRNA	Level of Efficiency	Non-Target Effects
Phosphophodiesters (antisense RNA and DNA, dsRNA)	Moderate	Moderate	Moderate	Moderate	Moderate
First generation (phosphorothioates, methylphosphonates)	Moderate	Higher nuclease stability	Lower binding capacity	Higher effectiveness	More pronounced non-specific effects
Second generation (2′-O-methyl and 2′-O-methyloxyethyl oligonucleotides)	Moderate	Much higher nuclease stability	Higher binding capacity	Higher effectiveness	More pronounced non-specific effects
Third generation (locked nucleic acids, peptide nucleic acids, morpholino oligomers)	Higher penetration ability	Nuclease resistant	Much higher binding capacity	Much higher effectiveness	Moderate