Blog 28 Apr 2023 

Big Concepts in Brief: What are Oligonucleotides?

Claire answers some of the most frequently asked questions about oligonucleotides, from a basic definition to their potential within the pharma industry.

Claire MacLeod

Claire MacLeod

Grand Challenge Lead
(she/her)

Oligonucleotides hold almost limitless potential for treating conditions like heart disease, cancer, and muscular dystrophy. But what exactly are oligonucleotides? And how do they work?

Traditionally, medicine evolved along the lines of one-size-fits-all’ treatments addressing most likely’ diagnoses. However, in recent years, personalisation has begun to challenge this convention. 

Also known as precision medicine, personalised medicine is tailored to the unique genetic makeup and physiological characteristics of individual patients. In theory, this approach could improve patient outcomes and minimise side effects. 

Among the groundbreaking innovations driving this trend forward, including advances in genome sequencing, sit revolutionary therapeutics like oligonucleotides.

What are oligonucleotides?

The word oligonucleotide consists of oligo’ — Greek for short’ — and nucleotide’ which refers to the building blocks of RNA or DNA. An oligonucleotide or oligo’ is a short, synthetic DNA or RNA strand.

How do oligonucleotide therapies work?

Illnesses and diseases tend to be caused by excesses or shortages of certain proteins in the body. Oligos, once inside the body, interact with specific strands of messenger RNA (mRNA) to translate the genetic information they carry into proteins. This has a therapeutic effect by either increasing the expression of specific proteins or targeting them to reduce or stop their expression.

When designing oligo therapies, scientists can modulate the nucleotide base to match the part of messenger RNA (mRNA) and the exact protein they want to modulate. In other words, new oligonucleotide therapies widen the scope of diseases we can treat, including rare diseases.

How are oligonucleotides made?

Oligonucleotides are manufactured using a complex, multistep chemical process where the oligo chain is grown through cyclical additions. This is followed by a complex purification process. 

This established process comes with limitations. For one, it is very resource-intensive and requires large quantities of solvent. Second, maximum scale of manufacture is limited making large volume production difficult. 

This is the industry’s grand challenge’: to develop an alternative process that is scalable, sustainable, and cost-effective. 

CPI’s Grand Challenge 3 project seeks to address this challenge by using liquid phase synthesis. This would remove the scale limitation and has the potential to reduce solvent volumes required. 

A more sustainable, less resource-heavy process would also make it possible to widen the application of oligonucleotides beyond rare diseases. 

Our partnership with AstraZeneca, Novartis, and The University of Manchester unites leading UK expertise in oligo synthesis to demonstrate the benefits of adopting an innovative approach to manufacturing oligonucleotides, and to deliver life-saving treatments more sustainably and economically. 

Building on the successes of these projects, we’re about to start construction of The Oligonucleotide Manufacturing Innovation Centre of Excellence to drive the future of research and development within oligonucleotide therapeutics. 

Collaboration across sectors is crucial to support the next generation of advances in healthcare, and at CPI we are actively playing our role. 

We’re hosting our 2nd Oligos Manufacturing Symposium event in April 2024

Register here

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