Overcoming Barriers for siRNA Therapeutics: From Bench to Bedside.
barriers to siRNA delivery
chemical modifications
endosomal escape
immune system activation
membrane impermeability
off-target effects
renal clearance
reticuloendothelial system entrapment
siRNA delivery systems
Journal
Pharmaceuticals (Basel, Switzerland)
ISSN: 1424-8247
Titre abrégé: Pharmaceuticals (Basel)
Pays: Switzerland
ID NLM: 101238453
Informations de publication
Date de publication:
07 Oct 2020
07 Oct 2020
Historique:
received:
19
08
2020
revised:
29
09
2020
accepted:
02
10
2020
entrez:
10
10
2020
pubmed:
11
10
2020
medline:
11
10
2020
Statut:
epublish
Résumé
The RNA interference (RNAi) pathway possesses immense potential in silencing any gene in human cells. Small interfering RNA (siRNA) can efficiently trigger RNAi silencing of specific genes. FDA Approval of siRNA therapeutics in recent years garnered a new hope in siRNA therapeutics. However, their therapeutic use is limited by several challenges. siRNAs, being negatively charged, are membrane-impermeable and highly unstable in the systemic circulation. In this review, we have comprehensively discussed the extracellular barriers, including enzymatic degradation of siRNAs by serum endonucleases and RNAases, rapid renal clearance, membrane impermeability, and activation of the immune system. Besides, we have thoroughly described the intracellular barriers such as endosomal trap and off-target effects of siRNAs. Moreover, we have reported most of the strategies and techniques in overcoming these barriers, followed by critical comments in translating these molecules from bench to bedside.
Identifiants
pubmed: 33036435
pii: ph13100294
doi: 10.3390/ph13100294
pmc: PMC7600125
pii:
doi:
Types de publication
Journal Article
Review
Langues
eng
Références
Nat Biotechnol. 2005 Jun;23(6):709-17
pubmed: 15908939
Methods Mol Biol. 2015;1218:1-15
pubmed: 25319642
EMBO J. 2002 Dec 16;21(24):6915-24
pubmed: 12486012
ACS Chem Biol. 2006 Apr 25;1(3):176-83
pubmed: 17163665
RNA. 2004 May;10(5):766-71
pubmed: 15100431
J Control Release. 2003 Aug 28;91(1-2):187-200
pubmed: 12932651
Drug Deliv Transl Res. 2013 Feb;3(1):84-99
pubmed: 25787868
Molecules. 2017 Oct 13;22(10):
pubmed: 29027965
Science. 2003 Aug 1;301(5633):640-3
pubmed: 12855817
Mol Ther. 2007 Sep;15(9):1663-9
pubmed: 17579574
Nucleosides Nucleotides Nucleic Acids. 2019;38(12):972-979
pubmed: 31298608
Gene Ther. 2011 Dec;18(12):1127-33
pubmed: 21490679
Nat Rev Immunol. 2002 Aug;2(8):569-79
pubmed: 12154376
Molecules. 2019 Jun 13;24(12):
pubmed: 31200490
RNA. 2019 Sep;25(9):1192-1201
pubmed: 31239298
Mol Ther. 2006 Apr;13(4):644-70
pubmed: 16481219
Immunology. 2017 Oct;152(2):232-242
pubmed: 28518215
J Control Release. 2014 Nov 10;193:270-81
pubmed: 24816071
J Control Release. 2007 Oct 8;122(3):209-16
pubmed: 17583369
J Extracell Vesicles. 2014 Aug 04;3:
pubmed: 25143819
Mol Biol Cell. 2002 Apr;13(4):1338-51
pubmed: 11950943
Proc Natl Acad Sci U S A. 2008 Oct 14;105(41):15908-13
pubmed: 18838694
Trends Mol Med. 2009 Nov;15(11):491-500
pubmed: 19846342
Nucleic Acids Res. 2013 Jul;41(12):6209-21
pubmed: 23620279
Nat Biotechnol. 2009 Sep;27(9):839-49
pubmed: 19701187
Nat Rev Drug Discov. 2010 Jan;9(1):57-67
pubmed: 20043028
Nucleic Acids Res. 2009 May;37(9):2867-81
pubmed: 19282453
Mol Pharm. 2009 May-Jun;6(3):659-68
pubmed: 19267452
Nat Biotechnol. 2004 Mar;22(3):326-30
pubmed: 14758366
Biotechnol Adv. 2019 Sep - Oct;37(5):801-825
pubmed: 31034960
Nat Biotechnol. 2005 Apr;23(4):457-62
pubmed: 15778705
Nature. 2006 Jan 5;439(7072):89-94
pubmed: 16306938
Nature. 2008 Apr 3;452(7187):591-7
pubmed: 18368052
Cancer Chemother Pharmacol. 2014 Feb;73(2):363-71
pubmed: 24297683
Oligonucleotides. 2009 Jun;19(2):89-102
pubmed: 19441890
Eur J Biochem. 1992 Dec 15;210(3):911-21
pubmed: 1483474
Asian J Pharm Sci. 2018 Jan;13(1):1-11
pubmed: 32104373
J Pharmacol Exp Ther. 2019 Sep;370(3):902-910
pubmed: 30940690
Chembiochem. 2007 Nov 23;8(17):2133-8
pubmed: 17924376
Gene Ther. 2006 Aug;13(16):1222-34
pubmed: 16625243
Biomater Sci. 2020 Mar 17;8(6):1759-1770
pubmed: 32010909
Theranostics. 2014 Jun 11;4(9):872-92
pubmed: 25057313
Int J Mol Sci. 2008 Mar;9(3):299-315
pubmed: 19325750
Gene Ther. 2005 Mar;12(5):461-6
pubmed: 15616603
Int J Pharm. 2010 Oct 15;398(1-2):219-24
pubmed: 20674725
J Drug Deliv. 2013;2013:374252
pubmed: 23533769
Nature. 2004 Nov 11;432(7014):173-8
pubmed: 15538359
Gene Ther. 2007 Jan;14(1):68-77
pubmed: 16915290
J Control Release. 2020 Jul 10;323:240-252
pubmed: 32272123
Transl Res. 2019 Dec;214:92-104
pubmed: 31404520
FEBS Lett. 2005 Jun 6;579(14):3115-8
pubmed: 15919084
Nat Rev Drug Discov. 2009 Feb;8(2):129-38
pubmed: 19180106
Nucleic Acids Res. 2007;35(17):5886-97
pubmed: 17726057
Nature. 2010 Jun 3;465(7298):584-9
pubmed: 20424607
Nature. 2001 May 24;411(6836):494-8
pubmed: 11373684
J Biol Chem. 2003 Nov 7;278(45):44826-31
pubmed: 12944394
Nat Commun. 2018 Feb 19;9(1):723
pubmed: 29459660
Nat Biotechnol. 2011 Apr;29(4):341-5
pubmed: 21423189
Nanomedicine (Lond). 2019 Jan;14(2):215-223
pubmed: 30511881
Hepatology. 2005 Jun;41(6):1349-56
pubmed: 15880588
Molecules. 2020 Jun 10;25(11):
pubmed: 32532030
Am J Physiol Renal Physiol. 2008 May;294(5):F1050-8
pubmed: 18305095
Nucleic Acids Res. 2003 Jun 1;31(11):2705-16
pubmed: 12771196
J Pharm Sci. 2009 Jan;98(1):74-80
pubmed: 18452181
Nanoscale. 2018 Aug 16;10(32):15339-15349
pubmed: 30070662
Oligonucleotides. 2009 Jun;19(2):191-202
pubmed: 19344210
Front Biosci (Landmark Ed). 2013 Jan 01;18:58-79
pubmed: 23276909
Nanomedicine. 2020 Oct;29:102239
pubmed: 32544449
Nature. 2001 Oct 18;413(6857):732-8
pubmed: 11607032
Science. 1990 Aug 3;249(4968):505-10
pubmed: 2200121
Curr Opin Mol Ther. 2010 Apr;12(2):158-67
pubmed: 20373259
Adv Drug Deliv Rev. 2012 Dec;64(15):1730-7
pubmed: 22732527
J Clin Oncol. 2014 Dec 20;32(36):4141-8
pubmed: 25403217
AAPS J. 2010 Dec;12(4):492-503
pubmed: 20544328
J Nucl Med. 2006 Apr;47(4):668-78
pubmed: 16595502
Oligonucleotides. 2009 Sep;19(3):209-22
pubmed: 19653880
Int J Pharm. 2006 Jan 3;307(1):93-102
pubmed: 16303268
Bioorg Med Chem. 2014 Apr 1;22(7):2320-6
pubmed: 24613624
Oligonucleotides. 2005 Fall;15(3):196-205
pubmed: 16201907
J Pathol. 1986 Mar;148(3):217-24
pubmed: 3009766
J Biophys. 2017;2017:1059216
pubmed: 28321253
RNA. 2007 Nov;13(11):1887-93
pubmed: 17804643
J Control Release. 2011 May 10;151(3):220-8
pubmed: 21078351
Nat Biotechnol. 2011 Apr;29(4):325-6
pubmed: 21478846
J Cell Sci. 2010 Apr 15;123(Pt 8):1183-9
pubmed: 20356929
Nat Biotechnol. 2017 Mar;35(3):222-229
pubmed: 28244992
Acc Chem Res. 2016 Jun 21;49(6):1242-9
pubmed: 27269119
J Am Chem Soc. 2014 Dec 10;136(49):16958-61
pubmed: 25434769
Clin Cancer Res. 2007 Apr 1;13(7):2207-15
pubmed: 17404105
Biotechnol Bioeng. 2007 Jul 1;97(4):909-21
pubmed: 17154307
Front Immunol. 2017 Mar 23;8:331
pubmed: 28386261
J Nucl Med. 2010 Jan;51(1):98-105
pubmed: 20008986
Biomedicines. 2017 Aug 09;5(3):
pubmed: 28792479
N Biotechnol. 2010 Jul 31;27(3):236-42
pubmed: 20219711
Cancer Biol Ther. 2009 Apr;8(7):594-8
pubmed: 19276660
Front Immunol. 2019 Dec 06;10:2860
pubmed: 31867014
Methods Enzymol. 2005;392:336-50
pubmed: 15644191
Adv Drug Deliv Rev. 2007 Mar 30;59(2-3):124-33
pubmed: 17459519
Hum Gene Ther. 2008 Feb;19(2):111-24
pubmed: 18230025
Eur J Pharm Sci. 2019 May 15;133:190-204
pubmed: 30946964
Arthritis Rheumatol. 2016 May;68(5):1099-110
pubmed: 26662519
Int J Clin Pharmacol Ther. 2012 Jan;50(1):76-8
pubmed: 22192654
Nucleic Acids Res. 2003 Jan 15;31(2):589-95
pubmed: 12527766
Nat Cell Biol. 2007 Jun;9(6):654-9
pubmed: 17486113
Nat Med. 2005 Mar;11(3):263-70
pubmed: 15723075
J Drug Deliv. 2017;2017:6971297
pubmed: 29218233
RNA. 2006 Jul;12(7):1179-87
pubmed: 16682560
Nature. 1998 Feb 19;391(6669):806-11
pubmed: 9486653
Nature. 2010 Apr 15;464(7291):1067-70
pubmed: 20305636
Nat Rev Mol Cell Biol. 2007 Jan;8(1):23-36
pubmed: 17183358
Proc Natl Acad Sci U S A. 2006 Sep 26;103(39):14373-8
pubmed: 16983097
Drug Discov Today. 2018 Apr;23(4):900-911
pubmed: 29373841
Mol Ther Nucleic Acids. 2013 Jul 02;2:e103
pubmed: 23820891
Nat Rev Drug Discov. 2019 Jun;18(6):421-446
pubmed: 30846871
Science. 2004 Aug 27;305(5688):1289-92
pubmed: 15297624
Nat Biotechnol. 2007 Oct;25(10):1149-57
pubmed: 17873866
Mol Ther Nucleic Acids. 2017 Mar 17;6:209-220
pubmed: 28325287
Chem Commun (Camb). 2010 Jan 21;46(3):392-4
pubmed: 20066302
Theranostics. 2013;3(3):201-9
pubmed: 23471415
Expert Opin Drug Deliv. 2009 Dec;6(12):1333-49
pubmed: 19941411
Annu Rev Immunol. 2019 Apr 26;37:349-375
pubmed: 30673536
Cell Commun Signal. 2013 Nov 18;11:88
pubmed: 24245560
Proc Natl Acad Sci U S A. 2001 Aug 14;98(17):9742-7
pubmed: 11481446
Nat Rev Drug Discov. 2015 Dec;14(12):843-56
pubmed: 26567702
J Blood Med. 2018 Aug 22;9:135-140
pubmed: 30174468
Drugs. 2020 Feb;80(3):335-339
pubmed: 32034693
Int J Mol Sci. 2012;13(1):516-33
pubmed: 22312268
Nat Biotechnol. 2005 Feb;23(2):222-6
pubmed: 15619617
Mol Ther. 2008 Apr;16(4):782-90
pubmed: 18362931
Biochem Biophys Res Commun. 2006 Apr 14;342(3):919-27
pubmed: 16598842
J Pharm Sci. 2007 Nov;96(11):2922-30
pubmed: 17518360
Clin Cancer Res. 2010 Aug 1;16(15):3910-22
pubmed: 20538762
Curr Cancer Drug Targets. 2008 Nov;8(7):554-65
pubmed: 18991566
Immunohorizons. 2020 Feb 21;4(2):93-107
pubmed: 32086319
Proc Natl Acad Sci U S A. 2014 Aug 5;111(31):11449-54
pubmed: 25049380
Cancer Gene Ther. 2016 Apr;23(4):73-82
pubmed: 26987292
Science. 2004 Sep 3;305(5689):1437-41
pubmed: 15284456
Cancer Discov. 2013 Apr;3(4):406-17
pubmed: 23358650
Nature. 2006 May 4;441(7089):101-5
pubmed: 16625202
Nat Biotechnol. 2006 Aug;24(8):1005-15
pubmed: 16823371
J Immunol. 2008 Mar 15;180(6):3729-38
pubmed: 18322178
Hum Gene Ther. 2006 Jul;17(7):751-66
pubmed: 16839274
ACS Chem Biol. 2015 May 15;10(5):1181-7
pubmed: 25730476
Adv Funct Mater. 2019 May 16;29(20):
pubmed: 31839764
J Control Release. 2008 Sep 24;130(3):266-74
pubmed: 18601962
Int J Nanomedicine. 2012;7:1525-41
pubmed: 22619510
Adv Drug Deliv Rev. 2007 Mar 30;59(2-3):101-14
pubmed: 17462786
Nucleic Acids Res. 2006 Mar 22;34(6):1669-75
pubmed: 16554553
J Ocul Pharmacol Ther. 2007 Oct;23(5):452-66
pubmed: 17900226
Cell Rep. 2018 Dec 18;25(12):3371-3381.e5
pubmed: 30566863
Nanomaterials (Basel). 2017 Apr 05;7(4):
pubmed: 28379201
Adv Pharmacol. 2014;71:245-75
pubmed: 25307219