Enhancing the stability of RNA Therapeutics to improve their delivery and efficacy using Deep Eutectic Solvents

SARS-CoV-2疫苗制定、批准和向英国公众推出的速度确实是惊人的，也是史无前例的。特别是，与基于蛋白质的疫苗相比，mRNA-LNPs的开发不仅非常快，而且非常有效，有望在100天或更短的时间内开创治疗/疫苗开发的新纪元。尽管取得了如此迅速的进展和前景，但mRNA-LNP技术的发展一直是速度和实用性之间的折衷；治疗/疫苗的不稳定已被证明是一个严重的缺点，需要超低温(-80℃)冷链，这直接增加了疫苗推出的成本和复杂性，并限制了高收入国家的疫苗接种计划。此外，由于信使核糖核酸的极端脆弱性，治疗/疫苗剂量取决于冷链的完整性。基于到目前为止的结果，我们相信我们可以通过开发一种通用的无毒稳定剂来克服许多制造瓶颈，如储存和分配，以及在常温下运输，这种稳定剂从制造到储存和运输到临床都能保护mRNA治疗/疫苗。我们相信，我们分子稳定剂的使用将从根本上改变RNA疗法/疫苗的市场，即使在缺乏功能冷链和分销系统的环境中，也可以生产、储存、运输和交付一致完整和高活性的RNA治疗/疫苗疗法。

The speed with which SARS-CoV-2 vaccines were formulated, approved and rolled out to the UK public has been truly remarkable and unprecedented. In particular the development of mRNA-LNPs proved not only very fast but also highly effective compared with protein based vaccines, promising a new era of therapeutic/vaccine development in 'one hundred days or less'. Despite such rapid progress and promise, the development of mRNA-LNP technology has been a compromise between speed and utility; instability of the therapeutic/vaccine has proved to be a serious drawback requiring an ultra low temperature (-80°C) cold-chain which has directly increased the cost and complexity of vaccine rollout as well as limiting vaccination programs in high income countries. Furthermore because of the extreme fragility of mRNA, the therapeutic/vaccine dose varies depending on the integrity of the cold-chain. Based on results to date we believe we can overcome many of the manufacturing bottlenecks such as storage and dispensing, as well as transport at ambient temperature by developing a universal non-toxic stabiliser that protects the mRNA therapeutic/vaccine from the point of manufacturing through to stockpiling and transport to the clinic. We are confident that the use of our molecular stabilisers will radically change the market for RNA therapeutics/vaccines by allowing the manufacture, storage, transport and delivery of consistently intact and highly active mRNA therapeutic/vaccine treatments even in environments that are lacking a functional cold-chain and distribution system.