Peptide-Functionalized Lipid Nanoparticles for mRNA Delivery to Restore FMRP in Fragile X Syndrome
Maryam Hajfathalian, PhD
Co-Principal Investigator
New Jersey Institute of Technology
Newark , NJ
Michelle James, PhD
Co-Principal Investigator
Md Emranul Karim, PhD
FRAXA Postdoctoral Fellow
Stanford University
Stanford, CA
2026-2027 Grant Funding: $200,000
Summary
Researchers at the New Jersey Institute of Technology and Stanford University are developing lipid nanoparticles, tiny delivery particles, to carry FMR1 messenger RNA (mRNA) into brain cells. This mRNA provides instructions for making FMRP, the protein missing or reduced in Fragile X syndrome. In laboratory-grown nerve cells, the team will test how effectively these particles deliver the mRNA and whether the cells produce FMRP.
The goal is to establish a foundation for a potential treatment that addresses the underlying cause of Fragile X.
The Science
Fragile X syndrome (FXS), the most common inherited neurodevelopmental disorder, is caused by the loss of Fragile X messenger ribonucleoprotein (FMRP), leading to impaired neuronal signaling, synaptic dysfunction, and neurobehavioral abnormalities. Although FXS is a strong candidate for mRNA-based therapy due to its monogenic nature, effective delivery across the blood–brain barrier (BBB) remains a major challenge.
In this project, the researchers will develop a non-viral, peptide-functionalized lipid nanoparticle (LNP) platform for targeted delivery of FMR1 mRNA to the central nervous system. Using Fragile X neuronal in vitro models, the team will investigate neuronal uptake, mRNA translation efficiency, FMRP restoration, dendritic protein synthesis, and mGluR5-associated signaling. These studies will be supported by radiolabeled LNP tracking and high-resolution cellular imaging.
The project will test whether targeted FMR1 mRNA delivery can restore FMRP production and improve molecular and cellular function in Fragile X models.