Oligonucleotide Therapeutics: A Biopharmaceutical Basics Overview

This is the fourth blog post in the Biopharmaceutical Basics series.

Over the past 30 years, noteworthy progress has been made in the field of oligonucleotide therapeutics, beginning with antisense oligonucleotides (ASOs) and aptamers, followed by siRNAs about 15 years ago. Today, recent innovations in the gene editing field are driving the need for oligonucleotides characterization.

If you’re new to the world of biopharma analysis, here’s a helpful overview of oligonucleotide therapeutics and what solutions are available today.

Why are oligonucleotides important?

Unlike the bulk of biologic drugs, which target proteins (and thus the downstream effects of diseases), oligonucleotides target errors in the genetic code — the root causes of diseases. Oligonucleotides are used for rare disorders that have been previously untreatable, such as neural and neuromuscular conditions. They allow for the development of therapeutics that affect protein targets that cannot be effectively treated by small-molecule or protein therapeutics.

Side effects for many oligonucleotides are more controllable and minimal than the side effects experienced with other classes of drugs. In addition, when compared to small-molecular drugs and large-molecule biopharmaceuticals, oligonucleotide therapeutics are much more straightforward to both design and develop.

What are oligonucleotides used for?

As reported by Ryszard Kole, Ph.D, in 1993, oligonucleotides can be used to modulate pre-mRNA splicing. Much work has been done to develop therapies targeting Duchenne muscular dystrophy, including progress treating the splicing mutation that causes Duchenne muscular dystrophy. These learnings hold much promise for a number of other conditions, as well.

What are enabling technologies for oligonucleotide therapeutics?

Advancing analytical methods that better characterize and quantitate both the oligonucleotide of interest as well as any synthesis contaminants, have been critically important enabling technologies. For example, new LC-MS methods have been introduced that use both low levels of trimethylamine (TEA) and hexafluoroisopropanol (HFIP) as a mobile-phase additive, providing good separation and reasonable mass spectrometry (MS) sensitivity. Advances in MS performance and data processing software dramatically improved data quality and simplified overall workflow, enabling scientists and researchers to accelerate development with the resolution and richness of characterization that mass spectroscopy offers.

How do Thermo Fisher solutions fit into the world of oligonucleotide therapeutics?

The analysis of oligonucleotide therapeutics requires robust and accurate analytical characterization to confirm identity, and to determine purity, quality and strength. Methods for accurate characterization that are capable of separating and identifying impurities must be established. Thermo Fisher Scientific offers these optimized solutions for characterizing: