RNA–lipid nanoparticles for acute critical illnesses

The runaway success of the COVID-19 RNA–lipid nanoparticle (LNP) vaccine has set off a ‘gold rush’ to apply RNA–LNPs to other diseases, with an estimated value of US$50 billion and tremendous investment by industry and government in the last few years. Moving beyond vaccines, the natural focus for the field of nanomedicine has been cancer, for which most previous nanomedicines were developed. However, great opportunities lie outside cancer, especially among acute, deadly diseases such as stroke and heart attack, where the short-term expression of therapeutic mRNA fits well with the disease time course. Here, we review those opportunities, with a special focus on aspects of RNA–LNPs that present challenges for these non-malignant diseases. For example, the adjuvanticity of LNPs that helps in vaccines becomes unwanted inflammation when delivering therapeutics. In particular, we focus on safety issues that must not be ignored if RNA–LNPs are to avoid the deadly mistakes that risk setting the field back decades. By remaining clear-eyed about these challenges, we can use the multi-component, semi-modular nature of RNA–LNPs to create a new class of therapeutics that benefits dozens of diseases and injuries. Beyond vaccines, RNA–lipid nanoparticle (LNP) nanomedicines have originally focused on cancer applications. This Review discusses how these therapeutics can also benefit acute critical illnesses (ACIs) owing to the short-term expression of mRNA while mitigating the adjuvant effect of LNPs, which, unlike in vaccines and cancer, can be a liability for ACIs.