Abstract
Following the first proof of concept of using small nucleic acids to modulate gene expression, a long period of maturation led, at the end of the last century, to the first marketing authorization of an oligonucleotide-based therapy. Since then, 12 more compounds have hit the market and many more are in late clinical development. Many companies were founded to exploit their therapeutic potential and Big Pharma was quickly convinced that oligonucleotides could represent credible alternatives to protein-targeting products. Many technologies have been developed to improve oligonucleotide pharmacokinetics and pharmacodynamics. Initially targeting rare diseases and niche markets, oligonucleotides are now able to benefit large patient populations. However, there is still room for oligonucleotide improvement and further breakthroughs are likely to emerge in the coming years. In this review we provide an overview of therapeutic oligonucleotides. We present in particular the different types of oligonucleotides and their modes of action, the tissues they target and the routes by which they are administered to patients, and the therapeutic areas in which they are used. In addition, we present the different ways of patenting oligonucleotides. We finally discuss future challenges and opportunities for this drug-discovery platform.
Highlights
The development of new drugs requires two major steps: the identification of a therapeutically relevant target and the development of a compound capable of modulating its function
The development of therapeutic oligonucleotides has required major evolutions to move from an attractive concept to the emergence of a new class of therapeutic agents
The initial promise of oligonucleotides was to be able to modulate any therapeutic target by modulating its expression level, which would make almost all therapeutic targets potentially druggable
Summary
The development of new drugs requires two major steps: the identification of a therapeutically relevant target and the development of a compound capable of modulating its function. Pharmaceutics 2022, 14, 260 activation can be achieved using a specific class of oligonucleotide called small activating RNA (saRNA) through direct interaction with gene promoters [3] Since they execute their function by complete Watson–Crick base pairing with DNA or RNA, oligonucleotides can in theory target any gene of interest since only the right nucleotide sequence along the targeted DNA or RNA needs to be selected. This considerably expands the number of proteins that can be targeted through the modulation of their mRNA expression. 44 companies have molecules on the market or in late clinical development (past phase II) These include oligonucleotide-focused biotech companies like Ionis. We present the different ways of patenting oligonucleotides and how two of the world’s leading patent offices assess inventions relating to oligonucleotides
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