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36 Pharmaceutical Technology ® The Real Message Behind Commercial mRNA Products April eBook 2023 PharmTech.com NOBEASTSOFIERCE - STOCK.ADOBE.COM F or several years after Crick (1) first described the genetic role of RNA, this molecular enti- ty was perceived simply as an "inert" carrier between DNA and protein. Today, howev- er, this view has almost entirely changed, and RNA- based molecules have been implicated in a broad range of functions including the activation/deacti- vation of genes, the excision of genetic material, and the transport of intercellular components. Indeed, it is expected that in the coming years, further discov- eries will uncover even greater biochemical signifi- cance to this molecular type. Given the ubiquity and variety of roles associated with RNA, it was inevitable that it would become a focus for investigators involved in the development of therapeutics. As early as 1978, Zamecnik (2) described the therapeutic use of an RNA-based oligonucleotide to inhibit replication of the Rous sarcoma virus, and, today, there are approximately 16 FDA-approved RNA therapies, 28 in clinical development, and many more expected in the near future (3). Currently, RNA-based medicines can be segregated by their functionality and structure and include spe- cies, such as messenger RNA (mRNA), antisense oligo- nucleotides (ASO), small interfering RNA (siRNA), and microRNA (miRNA). Other types of RNA include aptam- ers which are single-stranded and form higher-order structures, and more recently described, circular RNA (circRNA or oRNA), which appears to have multiple func- tions prior to and following the transcription process (4). Additionally, mature clustered, regularly interspaced, short palindromic repeats RNA (crRNA) and trans-acti- vating CRISPR RNA (tracrRNA) constitute components of the recently developed CRISPR technology. Challenges to development While not unique, the use of RNA in therapeutic ap- plications is generally incumbered by two key issues: The Marriage of RNA and Mass Spectrometry Mark Rogers is global scientific director at SGS. Considerable efforts have been made over the years to resolve the key issues of stability and delivery of RNA-based therapeutics.