What are oligos?
Oligos
Oligos or oligonucleotides are short, single stranded or double stranded fragments of DNA or RNA. These are synthetically made and customisable constructs, typically 13-25 nucleotides in length, however, depending on the application the length of these constructs can vary up to 200 nucleotides in length. These small molecules are incredibly powerful and are a versatile tool utilised in molecular biology.
Uses of oligos in biology
Oligos are commonly used in the study of genetics and in molecular biology. One of their most notable functions is their role in PCR, polymerase chain reaction, where oligos are DNA primers. These primers are customizable to target a specific DNA sequence and then act as the starting blocks for DNA synthesis. This is the technique used to amplify and generate many copies of a DNA sequence which can then be used in downstream techniques, it is often utilised in diagnostics, forensics, research, and cloning.
Oligos have been used in gene editing. CRISPR based genome editing can utilise these short oligo sequences to target a DNA sequence, allowing scientists to remove, edit, or insert customised sequences into parts of the targeted DNA sequence. This technique has huge benefits in research, and increasing uses in treatments of diseases, an example of this is a treatment for sickle cell anaemia.
Oligos have also been utilised as a pharmaceutical drug type, used to inhibit or activate gene expression or by inhibiting protein function. This has led to the success in the treatment of a variety of diseases such as a number of metabolic and neurological disorders.
What tools can we use to study oligos?
Oligos have many functions both in research and in the pharmaceutical industry. Characterizing these molecules can be very important in understanding their function and stability. Some tools offered at Malvern Panalytical to help with the study and characterization of oligos are:
- MicroCal ITC: Isothermal Titration Calorimetry (ITC). Label-free measurement of the binding affinity and thermodynamics of biomolecular interactions to understand function and mechanisms at a molecular level.
- MicroCal DSC: Differential Scanning Calorimetry (DSC). Offering confident characterization of macromolecule thermal stability
- WAVEsystem: Grating-Coupled Interferometry (GCI). Determine the binding kinetics and binding affinity of your biomolecules.
- OMNISEC: Multi-detection Size Exclusion Chromatography (SEC). Measure molecules absolute molecular weight, size, conformation, composition, and purity. Gaining insights into aggregation and stability.
- Zetasizer: Dynamic light scattering (DLS). Size characterization of molecules, identifying aggregation.
Reference
Dias, Nathalie, and C. A. Stein. “Antisense oligonucleotides: basic concepts and mechanisms.” Molecular cancer therapeutics 1, no. 5 (2002): 347-355.
Harris, E., 2024. Sickle cell disease approvals include first CRISPR gene editing therapy. JAMA, 331(4), pp.280-280.
Moumné, L., Marie, A.C. and Crouvezier, N., Oligonucleotide therapeutics: from discovery and development to patentability. Pharmaceutics. 2022; 14 (2): 260.