Oligonucleotides simply explained
October 25, 2024
Table of contents
ShowWhat are oligonucleotides?
Oligonucleotides (also referred to as oligos) are short nucleic acid polymers, made up of a strand of DNA or RNA. They are synthetically made and used for a variety of research, diagnostics, and therapeutic applications.
What is the difference between a nucleotide and an oligonucleotide?
Nucleotides are the basic building blocks that make up the nucleic acids DNA and RNA. A nucleotide is made up of a sugar molecule attached to a phosphate group and a nitrogenous base.
- In DNA, the sugar molecule is deoxyribose, and the resulting nucleotide is referred to as a deoxyribonucleotide.
- In RNA, the sugar molecule is ribose, and the resulting nucleotide is referred to as a ribonucleotide.
An oligonucleotide is a short chain of nucleotides, usually up to about 20 nucleotides long.
In biopharmaceutical manufacturing, nucleotides are used as raw materials for creating oligos, i.e., long chains of nucleic acids. For manufacturing purposes, it is essential to obtain nucleotides of high purity for the reliable synthesis of oligonucleotides. Oligonucleotides are synthesized by linking nucleotides together in precise sequences, either via chemical synthesis or by using enzymes. This process requires rigorous purification and quality control to ensure oligos are made up of the correct sequences and that they have the appropriate stability and functionality for therapeutic use.
Types of oligonucleotides
There are various types of oligonucleotides, each with their own structures and functions:
- DNA oligonucleotides are made up of deoxyribonucleotides. They are stable and very useful for a variety of molecular biology techniques. For example, they are commonly used in polymerase chain reaction (PCR), as primers to initiate DNA synthesis or as probes to detect specific DNA sequences.
- RNA oligonucleotides are made up of ribonucleotides. They are generally used in research, for example research involving gene expression of RNA interference (RNAi) therapies. RNA oligonucleotides are less stable and degrade more easily than DNA oligonucleotides.
- Phosphorothioate oligonucleotides are DNA or RNA oligonucleotides in which an oxygen atom has been replaced by a sulfur atom. This makes these oligos more resistant to being broken down by enzymes called nucleases, which in turn makes them more stable in biological systems and thus very useful for therapeutic applications.
- Antibody-oligonucleotide conjugates are hybrid molecules in which an oligo is chemically attached (conjugated) to an antibody. This allows oligonucleotides to be targeted to specific cells or tissues, as the antibody can bind to a specific antigen on a cell.
What are the therapeutic applications of oligonucleotides?
Oligonucleotides have a variety of therapeutic applications [1]. They are particularly useful in treating diseases at the genetic and molecular level because of their ability to interact with and modify genetic material [2]. Oligos can be synthesized to target specific molecular biological processes, for example by interfering with DNA or RNA or by disrupting protein synthesis [3]. Therapeutic applications of oligos include:
- Supportive oligonucleotide therapy: this involves the use of oligos to support or complement other treatments. Antibody-oligonucleotide conjugates are an example of this, as the oligo can help target a drug more specifically to its target tissue, reducing side effects or improving the effectiveness of the drug.
- Immune system support: some oligos can stimulate the immune system, helping it to respond more effectively to infections or cancer.
- Modulating gene expression: antisense oligonucleotides bind to specific mRNA sequences, blocking the production of harmful proteins by preventing translation of the mRNA sequences into proteins.
- Reducing toxic effects: in some diseases, toxic RNA molecules accumulate and disrupt cellular functions. Antisense oligonucleotides can bind to these toxic RNA sequences and prevent them from exerting their toxic effects.
In summary, oligonucleotides are proving to be ever more useful tools for a variety of therapeutic applications. As we continue to increase our understanding of the fundamental molecular mechanisms of many diseases, the important role played by oligos is only likely to grow. To find out more about the manufacture of oligonucleotides, some of the associated challenges, and the solutions to these challenges, click below.
References
- Moumné, L., A.C. Marie, and N. Crouvezier, Oligonucleotide Therapeutics: From Discovery and Development to Patentability. Pharmaceutics, 2022. 14(2).
- Roberts, T.C., R. Langer, and M.J.A. Wood, Advances in oligonucleotide drug delivery. Nature Reviews Drug Discovery, 2020. 19(10): p.673-694.
- Smith, C.I.E. and R. Zain, Therapeutic Oligonucleotides: State of the Art. Annual Review of Pharmacology and Toxicology, 2019. 59: p.605-630.
