AI Article Synopsis
- Synthetic OligoNucleotides (ON) are emerging as effective therapeutic tools for targeting genetic expression in various diseases, but challenges exist in their controlled release.
- Researchers developed Lipid-OligoNucleotide (LON) conjugates that form stable hydrogels, characterized by unique properties observed through advanced imaging techniques.
- These LON conjugates allow for a longer release of therapeutic sequences after being administered under the skin, offering a new method for sustained delivery of oligonucleotides without the need for additional substances.
Article Abstract
Synthetic OligoNucleotides (ON) provide promising therapeutic tools for controlling specifically genetic expression in a broad range of diseases from cancers to viral infections. Beside their chemical stability and intracellular delivery, the controlled release of therapeutic sequences remains an important challenge for successful clinical applications. In this work, Lipid-OligoNucleotide (LON) conjugates stabilizing hydrogels are reported and characterized by rheology and cryo-scanning electron microscopy (cryo-SEM). These studies revealed that lipid conjugation of antisense oligonucleotides featuring partial self-complementarity resulted in entangled pearl-necklace networks, which were obtained through micelle-micelle interaction driven by duplex formation. Owing to these properties, the Lipid AntiSense Oligonucleotide (LASO) sequences exhibited a prolonged release after subcutaneous administration compared to the non-lipidic antisense (ASO) one. The LASO self-assembly based hydrogels obtained without adjuvant represent an innovative approach for the sustained self-delivery of therapeutic oligonucleotides.
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| http://dx.doi.org/10.1039/d1bm00273b | DOI Listing |
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