Project Portugal 2030

Summary

mRNA vaccines are regarded as the missing link to address vaccines’ limitations, mostly due to improved safety, highly efficient immune responses, and lower time-to-market demands. Being the first two vaccines to receive emergency (and then definitive) regulatory approvals worldwide, mRNA-based technologies were crucial to combat the COVID-19 pandemic [2]. This milestone marked a new era in human prophylaxis and therapeutics approaches. The mRNA space is expanding to cover a broader range of diseases, with various products already in phase III from Moderna and BioNTech [3,4]. The global mRNA market is foreseen to grow from USD 11.3 billion (2022) to USD 27.7 billion in 2032 [5], representing a significant share with relevant impact on global economies. One of the major challenges of mRNA vaccines is the lack of thermostability, requiring ultra-cold storage equipment, consequently increasing the cost of these products while severely constraining massive vaccination in areas of the globe with limited resources [7]. From a different point of view, poor medication adherence due to frequent dosing, pain and discomfort (for parenteral administration, the typical mRNA immunization route), and adverse effects, is a pervasive issue with considerable health and socioeconomic consequences. Needle phobia affects approximately one out of every five people, being estimated as the primary reason for non-compliance with recommended paediatric immunization schedules, and accounting as well for as many as 10% and 16% of all individuals expressing COVID-19 and influenza vaccine hesitancy [8]. Driven by the premises of high permeation ability across the stratum corneum [18] while enhancing RNA stability [10,11], the combination of ILs with biocompatible FDA-approved polymers to form ionogel patches offers tremendous potential as non-invasive transdermal drug delivery systems. The recent approval by FDA of the NDA application of MRX-5LBT (MEDRx and D. Western Therapeutics Institute, Inc), a new type of lidocaine patch based on the proprietary technology Ionic Liquid Transdermal System, reinforces both the safety and feasibility of ionogel patches for systemic drug delivery [17]. However, these approaches have been mostly restricted to synthetic drugs [17,19] and yet, to the best of our knowledge, have not been investigated for mRNA delivery. NEEDleFREE aims to disrupt the traditional administration route of mRNA vaccines by developing a new biocompatible ionogel patch targeting mRNA transdermal delivery. To achieve this goal, multidisciplinary in nature by crossing the boundaries between chemical engineering, medical biotechnology, materials science, and technology transfer activities, the following specific objectives were set-up: i) mRNA production by IVT; ii) implementation and validation of the l mRNA downstream process; iii) Fabrication of biocompatible ionogel patches able to preserve the biological activity of mRNAs and promote their transportation across the skin; iv) In vivo assessment of the efficacy of mRNA transdermally administered using ionogel patches; v) assessment if stringent cold chain logistics can be applied to store and transport mRNA vaccines; vi) contribute to the national scientific and economic ecosystem by leveraging the commercial potential of the developed technology, creating added-value through the publication of scientific manuscripts, filling of European patents and creation of a spin-off towards product valorization.