mRNA remedy affords a promising platform for growing extremely efficient and personalised remedies for various ailments. This research employed two methods—chemical lipidation and bodily lipid doping—to introduce lipid elements into modular lysine-histidine-based peptide programs, for growing economical, secure, environment friendly, and focused mRNA carriers and systematically investigating the consequences of peptide and lipid modules on mRNA supply effectivity each in vitro and in vivo. In vitro outcomes demonstrated that lipid elements considerably improved the mRNA encapsulation and transfection effectivity of peptides, whereas sustaining good biocompatibility. The chemical optimization technique yielded a exceptional 5.3-fold enhancement in transfection effectivity over the corresponding pure peptide system. Using a bodily technique, the top-performing formulation demonstrated a transfection effectivity superior to that of the pure lipid and 43.9 instances larger than its pure peptide counterpart. It additionally outperformed business reagents in mRNA expression depth. In vivo, the optimum bodily composite system, with simplicity, cost-effectiveness and security, enabled environment friendly lung-targeted mRNA supply, displaying nice potential for advancing mRNA remedy of lung-related ailments. This research offers a broader perspective on the design of useful peptide-based gene supply programs.
