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. 2023 Jan 18;15(2):320. doi: 10.3390/pharmaceutics15020320

Table 1.

Selected sequences of peptides, especially cell-penetrating peptides, that are studied for enhanced oligonucleotides delivery. The two main cellular mechanism of delivery used are direct penetration or energy-dependent endocytosis, described in the main text. Once internalized, some peptide sequences facilitate the endosomal escape.

Name Sequence Type Application Ref.
Hydrophobic
P4 LGAQSNF ASO (PS) SSO(2OMe) for DMD [140]
Polycationic
TAT RKKRRQRRR siRNA Neurodegenerative pathologies
Lung and Malignant glioma
[141,142,143]
ASO (PNA/PMO) bacteria & nematodecell lines [144,145]
pAnt RQIKIWFQNRRMKWKKGGC ASO (PNA/PS) bacteria & nematodecell lines [129,144]
PolyArg Rn (n = 6–18) optimal 8 to 10 siRNA Neurons and different cancers [146,147]
(KFF)3K KFFKFFKFFK ASO (PNA/LNA) Anti-bacterial [144,148]
(RXR)4 RXRRXRRXRRXRXR ASO (PMO) Anti-viral anti-bacterial [144,149,150,151,152]
B peptide (RXRRBR)2XB ASO (PMO) SSO of DMD DM1 [153,154,155,156,157,158]
Pip5e RXRRBRRXR-ILFQY-RXRBRXRB ASO (PMO) SSO of DMD, SMA [159]
Pip6a RXRRBRRXR-YQFLI-RXRBRXRB ASO (PMO) SSO of DMD, SMA [160,161,162,163]
Pip6b RXRRBRRXR-IQFLI-RXRBRXRB ASO (PMO) SSO of DMD, SMA [164,165]
Amphipathic
MPG-8 GALFLGFLGAAGSTMGAWSQPKKKRK siRNA Xenograft tumor model [166]
ASO Mammalian cells [167]
Pep-1 KETWWETWWTEWSQPKKRK siRNA Cells [168]
CADY GLWRALWRLLRSLWRLLWRA siRNA Several cancer cells [169]
ASO Anti-bacterial [170]
RICK KWLLRWLSRLLRWLARWLG siRNA H glioblastoma cells [171]
599 GLFEAIEGFIENGWEGMIDGWY(G)4(R)9K siRNA Oral cancer [172,173]
Pepfect6 AGYLLGK(ε-Mtt)INLKALAALAKKIL siRNA Cell lines (various) [174]

ASO, antisense oligonucleotide; SSO, splice-switching oligonucleotides; DMD, Myotonic dystrophy; DM1, Myotonic dystrophy type J; SMA, spinal muscular atrophy; PS, phosphorothioate; PNA, peptide nucleic acids; PMO, phosphorodiamidate morpholinos; LNA, locked nucleic acid, 2OMe, 2′-O-methyl; X, 6-aminohexanoic acid; B, beta-alanine.