An Overview of the Stability and Delivery Challenges of Commercial Nucleic Acid Therapeutics

Nucleic acid (NA)-based biopharmaceuticals have emerged as promising therapeutic modalities. NA therapeutics are a diverse class of RNA and DNA and include antisense oligonucleotides, siRNA, miRNA, mRNA, small activating RNA, and gene therapies. Meanwhile, NA therapeutics have posed significant stability and delivery challenges and are expensive. This article discusses the challenges and opportunities for achieving stable formulations of NAs with novel drug delivery systems (DDSs). Here we review the current progress in the stability issues and the significance of novel DDSs associated with NA-based biopharmaceuticals, as well as mRNA vaccines. We also highlight the European Medicines Agency (EMA) and US Food and Drug Administration (FDA)-approved NA-based therapeutics with their formulation profiles. NA therapeutics could impact future markets if the remaining challenges and requirements are addressed. Regardless of the limited information available for NA therapeutics, reviewing and collating the relevant facts and figures generates a precious resource for formulation experts familiar with the NA therapeutics' stability profile, their delivery challenges, and regulatory acceptance.

Automated summary

Nucleic acid (NA)-based biopharmaceuticals show promise as therapeutic modalities, but face challenges such as stability, delivery, and cost. This article discusses the opportunities and challenges in achieving stable formulations of NA with novel drug delivery systems. It reviews the progress in stability issues and highlights the significance of novel drug delivery systems for NA-based biopharmaceuticals and mRNA vaccines. The approved NA-based therapeutics by the EMA and FDA, along with their formulation profiles, are also discussed. Addressing the remaining challenges and requirements for NA therapeutics could have a significant impact on future markets. Despite limited information, reviewing and collating relevant facts and figures is a valuable resource for formulation experts familiar with the stability profile, delivery challenges, and regulatory acceptance of NA therapeutics.