|
Guide destruction of IRESs/RNAs via an RNAse H-dependent degradation mechanism, or prevent IRESs interaction with the components of the translation machinery (40S ribosomal subunits, ITAFs, etc.) |
Easy to design, prepare/obtain |
Reduced efficiency of delivery, low intracellular stability, may cause proinflammatory responses |
(31, 32, 35, 36, 41, 66) |
|
Prevent IRESs interaction with the components of the translation machinery (40S ribosomal subunits, ITAFs, etc.) |
Enhanced stability (these compounds are not substrates of RNAse H) |
Reduced efficiency of delivery may cause proinflammatory responses |
(31, 32, 35, 36, 41, 66) |
|
Prevent IRESs interaction with the components of the translation machinery (40S ribosomal subunits, ITAFs, etc.) |
Enhanced stability, enhanced affinity toward target RNA sequences |
Reduced efficiency of delivery, intracellular trafficking. May be toxic |
(36, 37, 67–71) |
|
Prevent IRESs interaction with the components of the translation machinery (40S ribosomal subunits, ITAFs, etc.) |
Enhanced stability, enhanced affinity toward target RNA sequences |
Reduced efficiency of delivery, intracellular trafficking. May be toxic |
(36, 37, 67–71) |
|
Sterically block target RNAs. Prevent IRESs interaction with the components of the translation machinery (40S ribosomal subunits, ITAFs, etc.) |
Enhanced stability, reduced toxicity |
Reduced efficiency of delivery, intracellular trafficking. Specificity may be an issue |
(42, 43) |
Antisense: siRNA, shRNA (RNAi) |
Guide destruction of target IRESs/RNAs or mRNAs coding for ITAFs via RISC-dependent mechanism |
Easy to design, prepare/obtain |
Reduced stability and efficiency of delivery. Specificity may be an issue. May activate PKR |
(41, 44–47, 72–75) |
RNA aptamers, ribozymes (Rz), DNAzymes (Dz) |
Cleave target IRESs/RNAs. |
High selectivity |
Design process may be complicated |
(48–53) |
Short peptides, small molecules |
Prevent IRESs interaction with the components of the translation machinery (40S ribosomal subunits, ITAFs, etc.) |
Considered as the preferred form of drug therapies. Allow lead optimization |
Sometimes mechanism of action is difficult to establish and characterize, e.g., when small molecules have been selected during high-throughput screening |
(54–62, 76–78) |