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.