Is mRNA Drug The Future of The Drug Industry?

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Gilles Besin*

Executive Director, Discovery, Affinivax, USA

Correspondence to: Besin G. Executive Director, Discovery, Affinivax, USA, E-mail: gilles.besin@affinivax.com

Received: April 10, 2020; Accepted: April 10, 2020; Published: April 15, 2020

Copyright: ©2020 Besin G. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Citation: Besin G. Is mRNA Drug The Future of The Drug Industry? J Clin Microbiol Immunol. 2020; 1(1):002.

Citation: Besin G. Is mRNA Drug The Future of The Drug Industry? J Clin Microbiol Immunol. 2020; 1(1):002

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The conventional view of RNA casts the intermediate molecule between DNA and protein and a passive conduit for information. And that’s how the most familiar form of RNA, messenger RNA, works. But only a negligible fraction of RNA molecules in cells are mRNAs. mRNA technology promises to turn our bodies into medicine-making factories. The concept of nucleic acid-encoded drugs was conceived over two decades ago when Wolff et al. demonstrated that direct injection of in vitro transcribed mRNA or plasmid DNA into the skeletal muscle of mice led to the expression of the encoded protein in the injected muscle. At that time, mRNA was not pursued further as mRNA is less stable than DNA and as at this time, scientists could isolate or get only small amounts of the material, which was then easily destroyed by RNA-chopping enzymes found on the skin and in the air. In addition to the stability issue, scientific and technological advances were required to overcome some obstacles associated with mRNA, like its short half-life and unfavorable immunogenicity. Besides, the biggest barrier to mRNA therapy has been and remains the delivery of mRNA to the correct place, to the correct tissue and the precise cells. Associated with the specific delivery, as mRNA is a transient molecule susceptible to degradation primarily through nuclease activity, efficient protection is additionally required. Recent research efforts in the field in the last years have been made, and the field has prioritized the lipid nanoparticle (LNP) formulations approach to protect and deliver mRNA. LNP delivery systems has been proven to sustain stability imparted through protection from nuclease degradation, to facilitate organ specificity, efficient cellular uptake, and to provide endosomal escape properties that can enhance the successful delivery of the mRNA cargo to the cytoplasmic site of action. Diverse examples of successful delivery of mRNA by using LNPs for therapeutic as well as vaccine applications recently lead to the launch of clinical trials.

Thanks to many dedicated work, settled and in the last decade, mRNA technology is been used to develop personalized cancer vaccines, as well as vaccines for infectious diseases like the Zika virus, or more recently SARS Co-2. And now, several mRNA industrial players are also exploring whether these types of treatment can be employed as proteinreplacement therapies for rare conditions like the blood- clotting disorder hemophilia or methylmalonic acidemia.

Nevertheless, one challenge stands: to develop mRNA as a biopharmaceutical, the industrial process of the mRNA technology platform is required. These issues could be less crucial for ex vivo in cell therapeutic applications as the industrial process can mimic partially the one developed for cell therapy. For in vivo, the required amounts are different and more important, and the manufacturing will call for more understanding of the pharmaceutical properties, which will be costeffective but altogether it should be straightforward. Under the shadow of disappointments and failures in the neighboring fields of other nucleic acids therapy (DNA and siRNA), the mRNA field has been advanced with appropriate caution. One of the first reasons is the novelty of this technology. Indeed, many risks are present here, particularly in terms of safety, mainly in clinical trials. Also, the business expectations can be exaggerated, and industry leaders and investments in such novel therapy could be prudent. The current ongoing clinical testing programs inspired some confidence, but it is early phase development for this field, so prudence is maintained.

So, then what is the power of mRNA therapy? The potential advantages of mRNA therapy range from the discovery of the precise sequence (immunogenic for vaccines or ‘immunosilent’ for gene therapy), to rapid response manufacturing. The nature of mRNA technology allows rapid refinement with almost limitless combinations of derivatives in the pursuit of optimization.

The past and future clinical experiences will allow us to accelerate the selection of the optimal construct and formulation for development. These trials will inform our understanding of the need to achieve the optimal balance in the quality attributes of the mRNA for vaccine or gene therapy. Overall, with significant advances in the right field, mRNA biology, delivery and industrial manufacturing, the mRNA technology should lead, upon sufficient investment, in the development of the novel drug industry shortly