Messenger RNA Engineered Therapeutics for treating Genetic disorders (MeET)

Background

The development of messenger RNA–based therapies has emerged from a growing recognition that many rare genetic disorders result from the absence or malfunction of critical proteins, which cannot be adequately addressed by conventional small molecules or enzyme replacement therapies. Unlike DNA-based approaches, mRNA can be designed to transiently produce therapeutic proteins directly within patient cells, offering rapid onset of action and the potential for modular design across diverse targets. This strategy is particularly appealing for conditions such as Neurofibromatosis type I or cystic fibrosis, where restoring deficient protein levels can fundamentally alter disease progression and patient quality of life. However, current modalities face significant hurdles that impede their clinical adoption. Unmodified mRNA is inherently unstable and prone to rapid degradation by nucleases, necessitating repeated dosing and robust cold‐chain logistics. Delivery systems often trigger innate immune responses or exhibit low transfection efficiency in target tissues, leading to suboptimal protein expression and off‐target effects. Manufacturing remains complex and costly, with batch‐to‐batch variability and stringent purification requirements. Together, these limitations undermine therapeutic durability, scalability, and broad patient access.

Technology Description

The platform combines tailored mRNA sequences with modified nucleotides and optimized untranslated regions to restore deficient proteins in rare genetic disorders. mRNA is synthesized via a cell-free transcription process and purified to yield high concentrations suitable for therapeutic use. These transcripts are encapsulated in lipid nanoparticles formulated from DSPC, cholesterol, DOTAP and DMG-PEG at precise molar ratios, then assembled using a low-temperature extrusion process and a magnetically assisted nozzle that ensures uniform particle size and stability. Critical formulation parameters—including 5ʹ caps, poly(A) tail length and GC content—are fine-tuned, and resulting nanoparticles are characterized by dynamic light scattering, gel retardation assays, cytotoxicity testing and functional reporter gene studies to confirm efficient delivery and protein expression. This approach stands out by merging scalable, on-demand manufacturing with enhanced mRNA integrity and delivery efficiency. The proprietary extrusion and mixing technologies minimize shear and thermal stress, improving stability during storage and transport. By enabling continuous production of customized mRNA-LNP medicines, it reduces development timelines and costs compared to traditional orphan drug pipelines. Its modular design allows rapid adaptation to other targets—from cystic fibrosis to neurodegenerative conditions—while maintaining high safety profiles and precise dosing.

Benefits

Targeted in situ production of therapeutic proteins directly in patient cells
Continuous, scalable on-demand manufacturing enabled by SMART extrusion
Cost-effective alternative to conventional orphan drug development
Enhanced safety through minimized heat and shear stress preserving mRNA integrity
Versatile delivery platform adaptable to various mRNA cargos and nanoparticle vehicles