Messenger RNA (mRNA) encoding base editors, along with single guide RNAs (sgRNAs), have emerged as a promising therapeutic approach for various disorders. However, there is still insufficient exploration in achieving targeted and efficient delivery of mRNA and sgRNA to multiple organs while ensuring high biocompatibility and stability in vivo. To address this challenge, we synthesized a library of 108 poly(β-amino) esters (PBAEs) by incorporating 100% hydrophobic side chains and end-caps with varying amines. These PBAEs were further formulated with other excipients, including helper lipids, cholesterol, and PEGylated lipids, to form polymer-lipid nanoparticles (PLNPs). Structure-function analysis revealed that eLog