1. Hydrogel based lipid-oligonucleotides: a new route to self-delivery of therapeutic sequences
- Author
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Charlotte Soulard, Palma Rocchi, Isabelle Svahn, Philippe Barthélémy, Alexandra Gaubert, Gaelle Vacher, Sébastien Benizri, and Etienne Gontier
- Subjects
0303 health sciences ,Chemistry ,Oligonucleotide ,medicine.medical_treatment ,Biomedical Engineering ,Oligonucleotides ,Hydrogels ,02 engineering and technology ,Oligonucleotides, Antisense ,021001 nanoscience & nanotechnology ,Controlled release ,Micelle ,Lipids ,03 medical and health sciences ,Biochemistry ,Duplex (building) ,Self-healing hydrogels ,medicine ,General Materials Science ,0210 nano-technology ,Adjuvant ,Intracellular ,Micelles ,030304 developmental biology ,Conjugate - 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.
- Published
- 2021