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Sequence-specific and Selective Recognition of Double-stranded RNAs over Single-stranded RNAs by Chemically Modified Peptide Nucleic Acids
Published on: September 21, 2017
Novel cationic amphiphiles as delivery agents for antisense oligonucleotides
R K DeLong1, H Yoo, S K Alahari
1Department of Pharmacology, University of North Carolina, Chapel Hill, NC 27599, USA.
Nucleic Acids Research
|August 24, 1999
Summary
Researchers developed novel "molecular umbrellas" for enhanced nucleic acid delivery. These agents significantly improve gene and oligonucleotide delivery into cells, even in serum, offering a promising advance for nucleic acid-based therapies.
Area of Science:
- Biochemistry
- Molecular Biology
- Drug Delivery
Background:
- Therapeutic applications of nucleic acids like genes and oligonucleotides are hindered by inefficient cellular uptake.
- Current methods for delivering nucleic acids to the cytoplasm and nucleus remain a significant challenge in nucleic acid-based therapy.
Purpose of the Study:
- To develop novel cationic amphiphiles for improved nucleic acid delivery into cells.
- To investigate the efficacy of these "molecular umbrellas" in enhancing gene and oligonucleotide delivery and pharmacological activity.
Main Methods:
- Synthesis of novel cationic amphiphiles incorporating cholic acid moieties linked via alkylamino side chains.
- Evaluation of amphiphile efficacy in gene and oligonucleotide delivery using reporter gene assays and flow cytometry.
- Assessment of intracellular delivery, nuclear localization, and pharmacological effectiveness of antisense oligonucleotides.
Main Results:
- A specific derivative, amphiphile 5, demonstrated optimal gene and oligonucleotide delivery.
- Amphiphile 5, as a component of cationic liposomes, increased reporter gene delivery by 4-5 log units.
- Amphiphile 5 alone enhanced oligonucleotide association with cells by 250-fold and showed nuclear accumulation, with effectiveness comparable to commercial agents, even in high serum concentrations.
Conclusions:
- Novel "molecular umbrella" amphiphiles effectively facilitate nucleic acid delivery into cells.
- Amphiphile 5 represents a potent agent for enhancing gene and oligonucleotide delivery, showing promise for therapeutic applications.
- These novel agents offer advantages over commercial delivery systems, particularly in challenging biological environments like high serum concentrations.
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