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Antisense oligonucleotides can be conjugated to cell-penetrating peptides (CPPs) to increase cellular uptake. (A) CPPs can be directly conjugated to charge-neutral oligonucleotides, such as PMOs or PNAs using direct covalent unions [35]. (B) The peptide sequence is usually positively charged and rich in arginine. Here, a cell-penetrating peptide comprising a hydrophobic core and two flanking regions enriched with cationic amino acids such as arginine or B-alanine is shown.
