Breaking the mold with RNA-a "RNAissance" of life science

Abstract

In the past decade, RNA therapeutics have gone from being a promising concept to one of the most exciting frontiers in healthcare and pharmaceuticals. The field is now entering what many call a renaissance or "RNAissance" which is being fueled by advances in genetic engineering and delivery systems to take on more ambitious development efforts. However, this renaissance is occurring at an unprecedented pace, which will require a different way of thinking if the field is to live up to its full potential. Recognizing this need, this article will provide a forward-looking perspective on the field of RNA medical products and the potential long-term innovations and policy shifts enabled by this revolutionary and game-changing technological platform.

Fig. 1. mRNA vaccine development: structure, research fields and areas, and key milestones.

A mRNA vaccine. Schematic representation of an mRNA vaccine illustrating the lipid bilayer encapsulating the single-stranded mRNA. B Research fields and areas. An overview of the key research fields associated with mRNA vaccines, comprising Gene & Drug Delivery, RNA biology, and RNA applications C Key milestones. Major advancements in three fields/areas, gene and drug delivery, RNA, and RNA applications, led to the approval of the first mRNA vaccines. RNA application milestones highlight RNA’s expansion into new therapeutic areas, including vaccines to target tumors; delivery of novel protein therapeutics and gene replacement therapies; cell lineage reprogramming; and gene-editing technologies. CRISPR clustered regularly interspaced short palindromic repeats, EUA emergency use authorization, IPSCs induced pluripotent stem cells, LNP lipid nanoparticle, mRNA messenger RNA, NP nanoparticle, sgRNA single guide RNA, TALEN transcription activator-like effector nucleases. “Created with BioRender.com”.

Fig. 2. Current RMP market.

Meta-analysis of the current RMP space lends visibility into the level of activity in the field as well as its recent trends. A The eras of biologics and RNA. Illustrative data shows the rapid market capitalization growth rate RMPs contrasted with the comparatively slower market capitalization growth rate of biologics. B Market capitalization by technology. The total market capitalization of companies with RNA technology assets (excluding diversified companies, such as Merck, Pfizer, and Sanofi) from 2018 to 2022 is broken down by RNA technology and is compared to the S&P 500. Numbers above each bar represent the number of companies included in the analysis and the total market capitalization for that year. The market capitalization for publicly traded companies was estimated by multiplying historical closing share prices on December 31^st for each year by the outstanding shares. This data was obtained from Yahoo Finance, accessed May 17, 2023. The data for the S&P 500 was obtained from Yahoo Finance and accessed May 17, 2023. Standard statistical methods were used in the analysis of the data. *Some 43 private companies working with mRNA raised ~ $1.6B in funding from 2021 to 2022. C Number of programs by RNA class in 2023. The total volume of preclinical and active clinical programs in January of 2023 is represented in descending order. Data was obtained from Beacon Intelligence, RNA dataset, accessed April 1st, 2023. Data View used in the RNA dataset was ‘Drug Data.’ D 2023 mRNA pipeline by therapeutic area. The number of mRNA programs in 2023; all phases of development are broken down by therapeutic area. Data was obtained from Beacon Intelligence, RNA dataset, accessed April 1st, 2023. Data View used in the RNA dataset was ‘Drug Data.’ ASO antisense oligonucleotide, Cap capitalization, CircRNA circular RNA, CV cardiovascular, gRNA guide RNA, Ph phase, siRNA small interfering RNA.

Fig. 3. Navigating key challenges for the development of RNA medical products.

Overview of the essential engineering challenges faced in the advancement of RNA-based medical products. These include achieving accurate timing and placement of therapeutic effects, overcoming supply chain and refrigeration issues, handling disease-specific difficulties, and developing the capacity to formulate intricate biomolecules like bacterial polysaccharides. “Created with BioRender.com”.