Related Experiment Video
Updated: Aug 12, 2026
08:29
Generation of Cationic Nanoliposomes for the Efficient Delivery of In Vitro Transcribed Messenger RNA
Published on: February 1, 2019
Conformation of oligodeoxynucleotides associated with anionic liposomes
1Department of Pharmaceutical Sciences, The University of Connecticut, Storrs, CT 06269-2092, USA.
Nucleic Acids Research
|November 1, 2000
Summary
Antisense therapeutics benefit from understanding how oligodeoxynucleotides interact with lipids. Divalent cations and DPPG liposomes induce unique, sequence-specific DNA conformations, potentially impacting cellular uptake.
Area of Science:
- Biochemistry
- Molecular Biology
- Drug Delivery
Background:
- Antisense therapeutics show promise but require better understanding of oligodeoxynucleotide (ODN) cellular processes.
- ODN interactions with lipid assemblies and the influence of divalent cations are critical for function.
- Cellular internalization and intracellular distribution mechanisms need further elucidation.
Purpose of the Study:
- To investigate conformational changes in phosphorothioate oligodeoxynucleotides (ODNs) when interacting with anionic liposomes (DPPG) in the presence of divalent cations.
- To determine if these conformational changes are sequence-specific and ion-selective.
- To explore the potential implications of these conformations for ODN function and cellular uptake.
Main Methods:
- Circular dichroism spectroscopy was used to analyze ODN conformation.
- Phosphorothioate ODNs were incubated with 1,2-dipalmitoyl-sn-glycero-3-phosphatidylglycerol (DPPG) liposomes in the presence of divalent cations (e.g., calcium).
- Conformational changes were compared to ODNs exposed to divalent cations or liposomes alone.
Main Results:
- Significant conformational changes in ODNs occurred only when both anionic DPPG liposomes and divalent cations were present.
- The observed conformational changes were sequence-specific and ion-selective.
- Circular dichroism spectra for one ODN in the presence of calcium and DPPG suggested a unique, previously unreported DNA structure, distinct from C-DNA.
Conclusions:
- Divalent cations mediate sequence-specific conformational changes in ODNs upon interaction with anionic liposomes.
- A unique conformation of liposome-associated ODNs was observed, suggesting single-stranded DNA can maintain structure when adsorbed to surfaces.
- These findings may be relevant to ODN cellular uptake, intracellular transport, and therapeutic function.
