Versatility of cell-penetrating peptides for intracellular delivery of siRNA

Figures & data

Table 1. Examples of various CPP types.

CPP name	Sequence	Origin	Class	References
HIV-1 TAT protein, TAT48-60	GRKKRRQRRRPPQ	Natural (HIV-1 TAT protein)	Cationic	(Joliot et al., 1991)
Penetratin, pAntp43-58	RQIKIWFQNRRMKWKK	Natural (Antennapedia Drosophila melanogaster)	Cationic	(Joliot et al., 1991; Derossi et al., 1994)
Polyarginines	Rn	Synthetic	Cationic	(Futaki et al., 2001)
HRSV	RRIPNRRPRR	Natural	Cationic	(Milletti, 2012)
AIP6	RLRWR	natural	Cationic	(Milletti, 2012)
MPG	GALFLGFLGAAGSTMGAWSQPKKKRKV	HIV glycoprotein 41/ SV40 T antigen NLS	Membranotropic CPP/Primary Amphipathic	(Morris et al., 2008)
Pep-1	KETWWETWWTEWSQPKKRKV	’’	Membranotropic CPP/Primary Amphipathic	(Heitz et al., 2009)
ARF(1-22)	MVRRFLVTLRIRRACGPPRVRV	Natural	Membranotropic CPP/Primary Amphipathic	(Milleti, 2012)
pVEC	LLIILRRRIRKQAHAHSK	Natural	Membranotropic CPP/Primary Amphipathic	(Elmquist et al., 2001)
Transportan	GWTLNSAGYLLGKINLKALAALAKKIL	Synthetic	Membranotropic CPP/Primary Amphipathic	(Pooga et al., 1998)
MAP17	QLALQLALQALQAALQLA	Synthetic	Secondary amphipathic α-helical	(Milletti, 2012)
VT5	DPKGDPKGVTVTVTVTVTGKGDPKPD	Synthetic	Amphipathic (β-sheet)	(Oehlke et al., 1997)
Bac7	RRIRPRPPRLPRPRPRPLPFPRPG	Synthetic	Amphipathic &AMPs (Proline rich)	(Sadler et al., 2002)
(PPR)n	(PPR)3, (PPR)4, (PPR)5, (PPR)6	Synthetic	Proline-rich amphipathic CPPs	(Milletti, 2012)
gH625	NH2-HGLASTLTRWAHYNALIRAF-CONH2	Natural (Glycoprotein gH of HSV type I)	Membranotropic CPPs	(Smaldone et al., 2013)
GALA	WEAALAEALAEALAEHLAEALAEALEALAA	Synthetic	Membranotropic CPP /Secondary amphipathic α-helical	(Milletti, 2012)
INF7	GLFEAIEGFIENGWEGMIDGWYGC	Influenza HA2 fusion peptide	Membranotropic CPP /Secondary amphipathic α-helical	(El-Sayed et al., 2009)
CADY	GLWRALWRLLRSLWRLLWRA	PPTG1 peptide	Membranotropic CPP /Secondary amphipathic α-helical	(Konate et al., 2010)
C105Y	CSIPPEVKFNKPFVYLI	Natural(1-Antitrypsin)	Hydrophobic	(Rhee & Davis, 2006)
PFVYLI	PFVYLI	Synthetic	Hydrophobic	(Rhee & Davis, 2006)
Pep-7	SDLWEMMMVSLACQY	CHL8 peptide phage clone	Hydrophobic	(Gao et al., 2002)

Table 2. Examples of CPP-siRNA delivery.

CPP	Interactions	Proposed mechanism	Target gene	Results	References
MPG&MPGΔ^NLS	Non-covalent	Non-endocytotic	Luciferase	Effective up to 80%-95%	(Simeoni et al., 2003)
Tat-LK15	Non-covalent	Endocytic	nNOS	Improving the stability of siRNA in serum, and downregulating the expression of nNOS effectively and specifically	(Peng et al., 2017)
pH responsive ACPP	Non-covalent	Endocytic	PLK-1	Selectivity towards tumor cells	(Xiang et al., 2017)
RICK	Non-covalent	Non-endocytotic	Luciferase & CyclinB1	Knockdown of the expression of luciferase ∼75% and 80% of endogenous CyclinB1	(Vaissière et al., 2017)
LMWP	Covalent	Non-endocytotic	EGFP	Improving siRNA delivery with high gene-silencing efficacy and low cytotoxicity	(Ye et al., 2017; Ye et al., 2018).
Modified Octa-arginine	Non-covalent	Endocytic	Survivin	Reduction of the gene expression up to ∼60%, and strong siRNA binding and delivery efficiency	(Li et al., 2015)
PF & NF (analogs of Transportan 10)	Non-covalent	Endocytic	Luciferase	Effective up to 65%-85%	(Veiman et al., 2013)
SPACE	Non-covalent	Endocytic	IL-10& GAPDH	Improving penetration of siRNA into skin, and enhanced internalization into epidermal keratinocytes	(Hsu & Mitragotri, 2011)
SHRss	Non-covalent	Endocytic	Luciferase	High efficacy, and low toxicity	(Tai et al., 2015)
gH625	Non-covalent	Non-endocytic	GFP	High efficacy, and limited cell toxicity	(Ben Djemaa et al., 2018)
RVG9R3LC	Non-covalent	Endocytic	Murine superoxide dismutase-1	Enhanced endosomal escape, high efficacy, and no significant cell toxicity	(Ullah et al., 2018)
BR2	Non-covalent	Endocytic	GFP	High transfection efficiency, specificity towards target cells, and no significant cytotoxicity	(Lee et al., 2018)
LKH-stEK	Non-covalent	Endocytic	CTGF	High gene knockdown efficiency, and enhanced endosomal escape	(Hyun et al., 2018)

Figure 1. Diagram of cellular uptake mechanisms.

Figure 2. Downregulation of luciferase (Luc2) gene (Pärnaste et al., 2017). Figure reproduced from the respective publisher.

Figure 3. Comparison of the pDNA condensation efficiency by PF14 and nsPF14 (Veiman et al.,2013). Figure reproduced from the respective publisher.

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