Abstract
Intracellular delivery is crucial not only in achieving effective oligonucleotide therapeutics but also for a wide variety of therapeutic strategies. In this study to elucidate the effects of the number of incorporated arginine residues on cell membrane permeability, we designed a series of peptide ribonucleic acids (PRNAs) that alternatingly incorporated 4, 8, or 12 arginine residues (PRR1-3) in the PRNA backbone for experimental verifications. Indeed, the cellular uptake efficiency and the aggregation properties turned out to be critical functions of the number of incorporated arginine residues. Thus, the optimized PRR2 that incorporates 8 arginines showed the most efficient cellular uptake ability, much higher than that of octaarginine, without accompanying cytotoxicity or aggregation.
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