Today’s cyclodextrin was a little gift under CarboHyde’s and GENEGUT’s Christmas tree.
This study identified the structural modifications that enhance gene delivery activity of a range of cationic amphiphilic CDs, including both β- and γ-CD.
Each CDs incorporated a C12 lipid chain on the primary face of the CD. On the secondary rim, at positions C2 and C3, either primary or tertiary amine groups.
A comparative in vitro study was conducted to assess the gene silencing efficacy of these nanoparticles using the luciferase reporter gene in A549-luc cells.
Gene silencing levels for both β- and γ-CDs increased when modified with a primary amine compared to a tertiary amine group at position C2. Gene expression inhibition was further improved when the CDs were functionalized with amine functionalities at positions C2 and C3.
Modification of the secondary side of γ-cyclodextrins with two sets of primary amine functionalities via a thiopropyl linker, as compared to a triazole linker, achieved up to 80% gene knockdown, regardless of dose.
Ayse Kont, Monique Mendonça, PhD, Milo Malanga PhD, Kristóf Felegyi, Andrew Lindsay, Michael Cronin, Mary Cahill, Caitriona O’Driscoll
