Search

Lipid nanoparticle (LNP)–based mRNA delivery holds promise for the treatment of inherited retinal degenerations. Currently, LNP-mediated mRNA delivery is restricted to the retinal pigment epithelium (RPE) and Müller glia. LNPs must overcome ocular barriers to transfect neuronal cells critical for visual phototransduction, the photoreceptors (PRs). We used a combinatorial M13 bacteriophage–based heptameric peptide phage display library for the mining of peptide ligands that target PRs. We identified the most promising peptide candidates resulting from in vivo biopanning. Dye-conjugated peptides showed rapid localization to the PRs. LNPs decorated with the top-performing peptide ligands delivered mRNA to the PRs, RPE, and Müller glia in mice. This distribution translated to the nonhuman primate eye, wherein robust protein expression was observed in the PRs, Müller glia, and RPE. Overall, we have developed peptide-conjugated LNPs that can enable mRNA delivery to the neural retina, expanding the utility of LNP-mRNA therapies for inherited blindness.

The study of a two-dimensional cellular automata (CA) able to perform density classification tasks for ρ = ½ is hereby presented. Results show that, for two-dimension tasks, a perfect rule does not exist. However, the experiments show a good performance even when radius of neighborhood is minimum. The inherent space sensibility of CA is exploited for textural binary classification. Communication properties of CA are observed from the viewpoint of second order cybernetics.