2026-10-15T09:44:58Z https://data.mendeley.com/oai

oai:data.mendeley.com/kch397zzpt.1 2019-01-17T22:55:58Z

Yang, Zhenjun Data for: Structural optimization and additional targets identification of antisense oligonucleotide G3139 encapsulated in a neutral cytidinyl-lipid combined with a cationic lipid in vitro and in vivo Mendeley Data Antisense oligonucleotides (ASOs) usually contain a fully phosphorothioate (PS) backbone, which possibly interacts with many genes and proteins under intracellular conditions. G3139 is an ASO that targets Bcl-2 mRNA and induces cell apoptosis. Here, we report a kind of cytidinyl-lipid combined with a cationic lipid (DNCA/CLD, molar ration, 28:3, named mix), which might interact with oligonucleotides via H-bond formation, pi-stacking and electrostatic interaction, accompanied by low zeta potentials. The IC50 value of G3139 delivered by mix-lipid reduced from above 20 uM to 0.158 uM for MCF-7/ADR, and exhibited stronger antiproliferation upon other cancer cell lines. In addition, PS modification in the 3'-half of G3139 (especial at positions 13-16) enhanced serum stability, target specificity and anticancer activity. Also, a locked nucleic acid (LNA) gapmer G3139 (LNA-G3139) showed superior antiproliferation (78.5%) and Bcl-2 mRNA suppression effects (85.5%) at 200 nM, mainly due to its high mRNA affinity. More apoptosis-associated targets were identified, and a lower level of non-specific protein binding (HSA) determined revealed that both antisense and aptamer mechanisms might simultaneously exist. A combination of a new delivery system and chemical modifications, such as in LNA-G3139, may have potential clinical application prospects in the future. Oblimersen Antisense Ma, Yuan Dataset doi:10.17632/kch397zzpt.1 oai:data.mendeley.com/kch397zzpt.1 Public Domain Dedication http://creativecommons.org/publicdomain/zero/1.0/ https://data.mendeley.com/datasets/kch397zzpt 2019-01-17T22:55:58Z 2019-05-06T00:00:00Z