Gaurav Sahay1
Oregon State University1
<br/> Quantitative nucleic acid encapsulation by lipid-based nanoparticles (LNPs) is often thought to be one of the main prerequisites for successful cargo delivery, as the lipid environment protects mRNA from degradation by external nucleases and assists in initiating delivery processes. However, here we report the delivery of mRNA via preformed vesicle approach (PFV-LNPs) that defies this precondition. PFV-LNPs possess superficial mRNA localization that proved exceptionally beneficial in delivering mRNA to the back of the eye. Successful delivery of GFP mRNA to retinal pigment epithelium and photoreceptors was observed in mice, non-human primates, and human retinal organoids. This approach was generally beneficial as indicated by improved EGFP transfection with PFV-LNPs containing benchmark lipids (We posit that the PFV architecture may be beneficial to transfect local targets like the back of the eye. We will also discuss the impact of surface modifications for LNP mediated gene editing.