Managing mRNA Instability

Oligonucleotide drug substances generally are unstable at room temperature, and some are also degraded in the presence of certain enzymes. That is why, in part, they are formulated using special delivery solutions such as lipid nanoparticles (LNPs). (These delivery technologies also facilitate entry of nucleotide APIs into target cells.) Degradation can occur via loss of terminal nucleotides or certain functional groups, oxidation, and other mechanisms. Oligonucleotide–oligonucleotide interactions that can occur at higher concentrations are an added concern. These instability issues must be managed throughout the entire manufacturing process.

The challenges are particularly great for messenger RNA (mRNA), which can be degraded by enzymes found commonly in the environment, temperature, and due to the overall shear sensitivity of the
long-chained molecule.

Read this article in Pharmaceutical Technology’s The Real Message Behind Commercial mRNA Products eBook.

Editor’s Note: This article was previously published in Pharmaceutical Technology 2022 46 (12).

About the author

Cynthia A. Challener, PhD, is a contributing editor to Pharmaceutical Technology®.

Article details

Pharmaceutical Technology
eBook: The Real Message Behind Commercial mRNA Products
April 2023
Pages: 50–52

Citation

When referring to this article, please cite it as Challener, C. A. Managing mRNA Instability During Formulation, Manufacturing, and Shipment. Pharmaceutical Technology's The Real Message Behind Commercial mRNA Products eBook (April 2023).