It is estimated that 50 million people worldwide live with neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and Huntington’s. Gene therapies can help slow or reverse their progression. However, delivering them to the brain is difficult because of the blood-brain barrier (BBB). The BBB is made up of brain endothelial cells and other glial cells that regulate selective permeability of molecules and ions from the blood into the brain. This prevents large drugs and their carriers from crossing into brain tissue.

Lipid Nanoparticles (LNPs) are promising candidates for delivering gene therapies. They are biocompatible, nano-sized spherical drug carriers made of specialized phospholipids and cholesterol encapsulating genetic cargo. They also mimic lipoproteins, which are spherical carriers of triglycerides and cholesterol in the body’s natural lipid delivery system. 

Lipoproteins display various proteins on their surface that promote cell adhesion and uptake into cells, including brain endothelial cells. These proteins can be adsorbed onto the surface of LNPs by incubation, allowing them to mimic lipoprotein properties for cell adhesion and endocytosis.

In this study, I will make LNPs and incubate them with various concentrations of each protein of interest. Protein adsorption will be quantified using Western blotting and ELISA. The functionalized LNPs will be tested on brain endothelial cells in transwell assays to determine cell adhesion and gene therapy delivery efficiency compared to controls. The results of this study will help evaluate LNPs as an effective delivery platform for gene therapy medications to treat CNS disorders.