Gene therapy has become a successful tool for treating inherited retinal diseases (IRDs). To date, recombinant adeno-associated virus (rAAV)- mediated delivery is the preferred method for gene transfer; however, its limited payload capacity restricts its use for treatment to causative loci under 5 kb. Recent advances in gene therapy tools have demonstrated the success of non-viral delivery vectors with lipid-based nanoparticles (LNPs) at the forefront. Owing to the SARS-CoV-2 vaccine, LNPs have already demonstrated clinical safety, however in regard to IRDs, the LNPs are limited to RPE and Muller glia cells, and their application has been limited to transient RNA delivery. Previously, we have reported that the introduction of N-Hydroxysuccinamide (NHS) functionalized PEG lipid (DSPE-PEG2K-NHS) to the LNPs (called LNPx) improved their overall transfection rate and widened their transfection efficiency to include not only RPE but photoreceptor cells. Taken together, this could expand LNP utility and allow for the treatment of many prevalent IRDs. Herein, we utilized LNPx to demonstrate the feasibility and safety of dsDNA delivery after subretinal injection into the murine retina, through a combination of multimodal in vivo imaging and post-mortem histology.