 Nucleic acid, Na-based biopharmaceuticals have emerged as promising therapeutic modalities. These drugs are based on RNA or DNA molecules and include antisense oligonucleotides, CERNA, mRNA, mRNA, small activating RNA, and gene therapies. However, these drugs present several stability and delivery challenges, making them costly to produce. In this paper, we review the current progress in addressing these challenges and the significance of novel drug delivery systems, DDSs, associated with NA-based biopharmaceuticals. We also highlight the European Medicines Agency, EMA, and US Food and Drug Administration, FDA, approved NA-based therapeutics with their formulation profiles. Finally, we discuss how these drugs could impact future markets if the remaining challenges and requirements are addressed. This article was authored by Rahul J. Engel and Weijia Feng. We are article.tv, links in the description below.