Recent advances in mRNA-LNP therapeutics: immunological and pharmacological aspects

Abstract

In the last decade, the development of messenger RNA (mRNA) therapeutics by lipid nanoparticles (LNP) leads to facilitate clinical trial recruitment, which improves the efficacy of treatment modality to a large extent. Although mRNA-LNP vaccine platforms for the COVID-19 pandemic demonstrated high efficiency, safety and adverse effects challenges due to the uncontrolled immune responses and inappropriate pharmacological interventions could limit this tremendous efficacy. The current study reveals the interplay of immune responses with LNP compositions and characterization and clarifies the interaction of mRNA-LNP therapeutics with dendritic, macrophages, neutrophile cells, and complement. Then, pharmacological profiles for mRNA-LNP delivery, including pharmacokinetics and cellular trafficking, were discussed in detail in cancer types and infectious diseases. This review study opens a new and vital landscape to improve multidisciplinary therapeutics on mRNA-LNP through modulation of immunopharmacological responses in clinical trials. Graphical Abstract

CD3‐T‐cell‐engager (TCE) therapies to overcome solid tumors: Beyond BiTEs

“…The latest mRNAlipid nanoparticles (LNPs) can deliver BiTE mRNA into tumor cells. 65 Thus, the development of BiTE-mRNAcarrying LNPs that specifically target tumor cells is also promising.…”

Regulatory safety evaluation of nanomedical products: key issues to refine

“…They are among the first cells, after neutrophilic leukocytes, to respond to an external challenge of the body. When we consider the particulate nature of nanomedicines that end up to a large extent in the phagocytizing macrophages, this offers opportunities for specific directed targeting to deplete macrophages by liposome-encapsulated clodronate for therapeutic purposes (Ravichandran et al [32]) or activate macrophages as antigen presenting cells for nanoformulated messenger RNA vaccines (Kiaie et al [33]). However, the macrophage homing can have consequences with regard to possible adverse effects of the nanomedicine like chronic activation of macrophages in COVID vaccines resulting in immune dysregulation (Ravichandran et al [32]).…”

How far are the new wave of mRNA drugs from us? mRNA product current perspective and future development

“…At the modification level, chemical modifications improve drug stability and reduce toxicity ( 72 ). At the level of delivery system synthesis and design, the synthesis of lipid nanoparticles mRNA-LNP is a key focus of R&D in the mRNA field ( 20 ). mRNA vaccine or drug scale-up production is highly reproducible, with successful sequence modification and delivery system assembly at the core.…”

“…The advantages of using an LNP delivery system include the following: the use of LNP removes the risk of infection, oncogenicity, and immunogenicity compared to viral vectors ( 83 ); LNP can be introduced into the target cell by decorating the cell surface with ligands; LNP prevents mRNA degradation and aids endocytosis and endosomal escape, thus enhancing antigen expression and the efficiency of mRNA vaccination; adjuvants can be added to LNP to aid immune activation and potential immune response ( 20 ).…”

“…Examples are TriMix-based immunotherapy (ECI-006), autologous cell therapy CAR-T MCY-M11 (MaxCyte), and Cartesian therapy ( 19 ). mRNA has the potential to prevent and treat a wide range of diseases, and as a breakthrough technology platform, is expected to partially replace traditional drugs and vaccines, opening up new therapeutic frontiers and revolutionizing new treatments ( 20 ).…”