RNA technologies: mechanisms of action, applications and forms of delivery
The aim of this report is to provide a technical and scientific overview of the various currently relevant RNA technologies. It provides information on the mechanisms of action of the various RNA-based approaches, their fields of application and products and their development status. The report is intended to help assess and discuss the benefits, risks and limitations of the various RNA technologies and their products. It is also intended to support the legal categorisation of RNA products.
Ribonucleic acids (RNA) play an essential role in all cells of all organisms. Nevertheless, until recently, these molecules were overshadowed by the much better-known deoxyribonucleic acid (DNA). It was only the COVID-19 pandemic that brought RNAs in the form of mRNA vaccines into the spotlight: less than a year after the outbreak of the pandemic, mRNA vaccines against SARS-CoV-2 were available in most western countries. This was the result of decades of research into both the structure and function of RNAs and their use in therapy. In Switzerland, around 70% of the population was vaccinated against SARS-CoV-2 in April 2023, the vast majority with an mRNA vaccine.
RNAs occur naturally in all cells and fulfil a wide variety of functions. They play a prominent role in the production of proteins, for example by transferring genetic information from the DNA in the cell nucleus to the cytoplasm via messenger RNAs (mRNAs). However, RNAs also fulfil many regulatory functions in cells and can bind to a variety of target molecules. This makes them potentially suitable for a wide range of applications, particularly in medicine and agriculture. RNA technologies, especially for therapeutic applications, have been developed for over 30 years. The first RNA-based therapies were authorised at the turn of the century. However, the technologies were not yetwidely accepted at that time. Only in recent years have decisive technical advances been made, for example by stabilising RNA and introducing it efficiently into target cells. As a result, several new RNA therapies have been developed within a few years and public and industrial research into RNA technologies has intensified considerably (Mollocana-Lara et al., 2021). With the success of the mRNA vaccines against SARS-CoV-2, RNA technologies have now moved even more into focus. Various research groups and networks, e.g. the Swiss National Center of Competence in Research RNA & Disease (NCCR RNA & Disease), as well as private companies, are also working on the research and development of RNA technologies, particularly in the field of therapeutics.
The RNA-based methods relevant to the report were identified on the basis of the specialist literature and assessments by experts and categorised into eight groups:
1. post-transcriptional gene silencing
2. mRNA technologies
3. RNA aptamers
4. long non-coding RNAs (lncRNA)
5. RNA-directed DNA methylation (RdDM)
6. RNA activation (RNAa)
7. circular RNAs (circRNAs)
8. ribozymes
The various RNA-based methods can differ in the type of RNA molecules used, the target molecules to which they bind and/or the mechanism of action. The distinction between the different methods is not always clear, and various categories and designations are also used in the literature. The grouping used here is therefore only one of several ways of categorising the different RNA technologies.
Source: Kümin M, Eyer K, Hall J, Koch A, Pascolo S, Romeis J (2024) RNA technologies: mechanisms of action, applications and forms of delivery. Swiss Academies Reports 19 (1)
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