Morpholinos and siRNA
In recent decades siRNA has supplanted phosphorothioate antisense as the method most investigators consider first for gene knockdowns in cultures or animals. However, as it was before with phosphorothioates, investigators have become frustrated with the experimental failures, the time and money required to screen sequences, the off-target expression modulation and the non-antisense effects associated with siRNA. Here you can read a 2007 paper discussing mechanisms, strengths and weaknesses of siRNA and phosphorothioate oligos versus Morpholino oligos: Summerton J. Morpholino, siRNA, and S-DNA Compared: Impact of Structure and Mechanism of Action on Off-Target Effects and Sequence Specificity. Med Chem. 2007;7(7):651-660 .
Morpholinos and other steric blocking antisense
Morpholinos are a form of steric blocking antisense, a mechanism Morpholinos share with some other antisense structural types including peptide nucleic acids (PNAs), 2'-O-substituted oligos (e.g. 2'-O-methyl phosphorothioates, 2'-O-methoxyethyl phosphorothioates) and locked nucleic acids (LNAs). These are all examples of RNase-H independent antisense, as discussed in this paper: Summerton J. Morpholino Antisense Oligomers: The Case for an RNase-H Independent Structural Type. Biochimica et Biophysica Acta 1999 1489: 141-158
Morpholinos are compared with peptide nucleic acids in this book chapter:
Summerton JE. Peptide Nucleic Acids, Morpholinos, and Related Antisense Biomolecules. Janson C. and During M., eds. Landes Biosciences 2004, Georgetown, TX.
Morpholinos and phosphorothioate antisense
Here you can read a 2007 paper discussing mechanisms, strengths and weaknesses of siRNA and phosphorothioate oligos versus Morpholino oligos: Summerton J. Morpholino, siRNA, and S-DNA Compared: Impact of Structure and Mechanism of Action on Off-Target Effects and Sequence Specificity. Med Chem. 2007;7(7):651-660
Morpholinos are compared with RNase-H dependent phosphorothioate antisense in this paper:
Summerton J, Stein D, Huang SB, Matthews P, Weller D, and Partridge M. Morpholino and Phosphorothioate Antisense Oligomers Compared in Cell-Free and In-Cell Systems. Antisense & Nucleic Acid Drug Development 1997; 7: 63-70.