Table 2. Selected recent publications on oligonucleotide delivery.
| Delivery approach | Summary | Significance | Reference |
|---|---|---|---|
| LNPs | Tested a large library of ‘lipoids’ for siRNA delivery in cells and in vivo | Discovered structural and pKa features for design of effective LNPs | (175) |
| Polymer NPs | Developed a hybrid lipid-polymer NP for siRNA delivery | Polymer NPs had excellent pharmacokinetic characteristics and were effective in silencing in a tumor model | (199) |
| Antibody-siRNA conjugates | THIOMAB monoclonals with siRNA conjugation at specific sites were used to test siRNA delivery | Highlights the variability and difficulty in using antibody-siRNA conjugates | (297) |
| Molecular scale ligand–oligonucleotide conjugates | Developed trivalent glycoconjugates targeting the ASGPR; these provided effective siRNA delivery to the liver | Exemplifies the advantages of conjugates including defined molecular properties, selectivity and efficacy | (258) |
| Macromolecular scale conjugates | Developed a targeted polymer-PEG-siRNA conjugate that was effective in delivery to the liver | This is the initial report on ‘dynamic polyconjugates’ which seem to be a promising approach for delivery | (300) |
| Delivery to the CNS | ASOs were used to antagonize a lncRNA involved in a neurodevelopmental disorder | Exemplifies effective use of ASOs in the CNS | (73) |
| DNA nanostructures | Developed tetrahedral DNA nanostructures incorporating siRNA with folate for targeting; these were effective in silencing both in cells and in a xenograft model | Provides a thorough study of the potential of using DNA nanostructures for oligonucleotide delivery | (330) |
| Basic studies: description of oligonucleotide uptake and subcellular trafficking | These three studies used advanced microscopic techniques to quantitatively analyze the uptake, trafficking and delivery of siRNAs | Provide important insights into the intracellular fate of oligonucleotides | (158,181,182) |
| Basic studies: role of the trafficking machinery in oligonucleotide pharmacology | Used shRNA libraries to identify genes important in determining the effectiveness of oligonucleotides; found that TSG101, an ESCRT component, is vital | Demonstrates that the intracellular trafficking machinery is a key determinant of oligonucleotide pharmacology | (152) |
| Small molecules for oligonucleotide delivery | Used high-throughput screening to identify compounds that dramatically enhance the pharmacological effectiveness of oligonucleotides both in cells and in vivo; these compounds act by releasing oligonucleotides from unproductive entrapment in late endosomes | Demonstrates that small molecules can be used to manipulate the intracellular trafficking of oligonucleotides in a beneficial manner | (336) |
A limited number of publications have been selected as excellent examples of oligonucleotide delivery strategies or of basic studies on delivery.