Organocatalyst streamlines oligonucleotide drug synthesis
Researchers at Shanghai Jiao Tong University have developed a new organocatalytic method to synthesize phosphorothioate oligonucleotides. This process replaces bulky, expensive molecular guides with a chiral catalyst, making the production of RNA-based drugs more efficient and scalable.
Why it matters
Improving the synthesis of oligonucleotide drugs could lower manufacturing costs and increase the availability of advanced RNA therapies for various diseases.
A new organocatalytic reaction offers a simpler way to make an important class of drugs based on modified nucleic acid chains. The catalyst eliminates the need for temporary molecular guides that are currently needed to control phosphorus stereochemistry during the synthesis of phosphorothioate oligonucleotides used in several approved RNA therapies.
Phosphorothioate oligonucleotides are short strands of DNA or RNA in which one oxygen atom in the phosphate backbone is replaced with sulfur. This makes the molecules more resistant to degradation inside the body and improves their ability to enter cells, and so is used in nearly every approved antisense oligonucleotide drug. But every sulfur substitution also creates a chiral phosphorus atom, meaning each linkage can exist in two mirror-image forms. Current manufacturing strategies produce both forms indiscriminately, generating mixtures of molecules whose biological activities can differ markedly.
Source: © Shuai-Shuai Fang et al/Springer Nature Limited 2026
Get smarter about the news
Sign up free for a feed built around what you actually care about, Dive Deeper research on any story, and the full text of every article.
Create free accountAlready have an account? Sign in