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Updated: Jun 23, 2026
09:04
Sequence-specific and Selective Recognition of Double-stranded RNAs over Single-stranded RNAs by Chemically Modified Peptide Nucleic Acids
Published on: September 21, 2017
Antisense oligonucleotide pharmacokinetics and metabolism
1Isis Pharmaceuticals, Inc., 1896 Rutherford Rd, Carlsbad, CA 92008, USA. rgeary@isisph.com
Expert Opinion on Drug Metabolism & Toxicology
|April 22, 2009
Summary
Understanding oligonucleotide pharmacokinetics is crucial for developing effective therapeutic agents. Backbone chemistry dictates biological stability and protein binding, influencing drug delivery and application.
Area of Science:
- Pharmacology
- Drug Delivery
- Biochemistry
Background:
- Oligonucleotides are gaining interest as therapeutic agents.
- Understanding their pharmacokinetic properties is essential for drug design and application.
Purpose of the Study:
- To review key pharmacokinetic properties influencing oligonucleotide use and delivery.
- To highlight factors critical for successful therapeutic applications.
Main Methods:
- Literature review focusing on pharmacokinetic data.
- Analysis of single-strand phosphorothioate antisense oligonucleotides and second-generation modifications.
- Comparative analysis with other oligonucleotide classes.
Main Results:
- Pharmacokinetic properties vary significantly across different oligonucleotide classes.
- Backbone chemistry is a primary determinant of pharmacokinetic behavior.
- Biological stability and plasma protein binding are key factors influenced by backbone chemistry.
Conclusions:
- Oligonucleotide therapeutic development relies heavily on understanding pharmacokinetic profiles.
- Backbone chemistry fundamentally shapes an oligonucleotide's stability and protein interactions.
- Tailoring backbone chemistry is vital for optimizing drug delivery and therapeutic efficacy.
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