title: Cellular endocytosis and gene delivery.
abstract: Endocytosis is the process by which cells take up macromolecules from the surrounding medium. The best-characterized process is the so-called clathrin-dependent endocytosis, although much is also currently known about clathrin-independent endocytic processes such as those involving caveolae and lipid rafts. An understanding of endocytosis and the cellular trafficking that occurs thereafter has a great deal of relevance to current molecular medicine. Gene therapy, which is presently being investigated for its therapeutic potential in treating immunodeficiency and metabolic diseases, cancer and heart disease, employs a variety of viral and nonviral vectors, which can be delivered to the target cells of the body and are subsequently endocytosed and dissembled. A variety of vectors can be used to deliver genes to organs in vivo or cells ex vivo. Various routes of vector delivery have been investigated. The mechanisms by which vectors such as adenoviruses, adeno-associated viruses, retroviruses and liposomes enter the cell are increasingly being investigated as the effort to increase the efficiency of gene therapy continues. This review focuses on mechanisms of endocytosis and how they relate to the internal trafficking of viral and nonviral vectors in gene therapy.
authors.affiliation: Boyer Center for Molecular Medicine, Yale University, New Haven, Connecticut, United States of America.
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Ziello
authors.forename: Yan
authors.initials: Y
authors.lastname: Huang
authors.forename: Ion S
authors.initials: IS
authors.lastname: Jovin
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D004247:DNA / Q000008:administration & dosage; D004705:Endocytosis / Q000502:physiology*; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006801:Humans; D051379:Mice
chemical_list: D004247:DNA
references.citation: Curr Biol. 2007 Jul 3;17(13):1151-6
references.pmid: 17600709
references.citation: Science. 1999 Jul 9;285(5425):215-20
references.pmid: 10398591
references.citation: Annu Rev Biomed Eng. 2006;8:343-75
references.pmid: 16834560
references.citation: Traffic. 2002 Jul;3(7):443-51
references.pmid: 12047552
references.citation: Trends Cell Biol. 1995 Nov;5(11):424-8
references.pmid: 14732047
references.citation: Cell. 1984 Jul;37(3):789-800
references.pmid: 6204769
references.citation: Traffic. 2006 May;7(5):549-61
references.pmid: 16643278
references.citation: J Cell Sci. 1996 Dec;109 ( Pt 12):2905-14
references.pmid: 9013338
references.citation: Proc Natl Acad Sci U S A. 1995 Oct 24;92(22):10339-43
references.pmid: 7479780
references.citation: Gene Ther. 2000 Jul;7(13):1156-65
references.pmid: 10918483
references.citation: J Clin Invest. 2008 Sep;118(9):3132-42
references.pmid: 18688285
references.citation: Science. 1996 Jan 19;271(5247):363-6
references.pmid: 8553074
references.citation: Nat Biotechnol. 2008 Apr;26(4):431-42
references.pmid: 18376398
references.citation: Life Sci. 2008 Nov 21;83(21-22):747-55
references.pmid: 18930744
references.citation: Nat Cell Biol. 2006 Jan;8(1):46-54
references.pmid: 16341206
references.citation: J Clin Oncol. 2002 Mar 15;20(6):1668-76
references.pmid: 11896118
references.citation: Annu Rev Biochem. 1998;67:199-225
references.pmid: 9759488
references.citation: Exp Cell Res. 2000 Mar 15;255(2):221-8
references.pmid: 10694437
references.citation: J Biol Chem. 1997 May 16;272(20):13419-25
references.pmid: 9148966
references.citation: Hum Gene Ther. 2003 Jul 20;14(11):1079-88
references.pmid: 12885347
references.citation: Proc Natl Acad Sci U S A. 2002 May 28;99(11):7594-7
references.pmid: 12032328
references.citation: Proc Natl Acad Sci U S A. 2007 May 1;104(18):7594-9
references.pmid: 17463083
references.citation: Semin Cell Dev Biol. 2002 Jun;13(3):205-14
references.pmid: 12137741
references.citation: Nat Rev Cancer. 2003 Jul;3(7):477-88
references.pmid: 12835668
references.citation: Nat Med. 2004 Mar;10(3):310-5
references.pmid: 14770178
references.citation: Expert Opin Drug Deliv. 2008 Feb;5(2):189-204
references.pmid: 18248318
references.citation: J Biol Chem. 2003 Nov 7;278(45):44826-31
references.pmid: 12944394
references.citation: J Cell Biol. 1987 Oct;105(4):1623-35
references.pmid: 3667693
references.citation: Science. 1997 Feb 28;275(5304):1320-3
references.pmid: 9036860
references.citation: J Cell Biol. 1998 Feb 9;140(3):591-601
references.pmid: 9456319
references.citation: J Cell Biol. 1998 Apr 6;141(1):101-14
references.pmid: 9531551
references.citation: FEBS Lett. 1996 Jun 24;389(1):48-51
references.pmid: 8682204
references.citation: J Control Release. 2001 Jul 6;74(1-3):95-113
references.pmid: 11489487
references.citation: J Gene Med. 2005 Oct;7(10):1335-47
references.pmid: 15945120
references.citation: Gene Ther. 2005 Jul;12(14):1089-98
references.pmid: 16003340
references.citation: Bioconjug Chem. 2004 Nov-Dec;15(6):1246-53
references.pmid: 15546190
references.citation: J Biol Chem. 1989 Dec 5;264(34):20163-6
references.pmid: 2479645
references.citation: Mol Biol Cell. 2005 Feb;16(2):964-75
references.pmid: 15601897
references.citation: J Clin Invest. 2008 Sep;118(9):3143-50
references.pmid: 18688286
references.citation: J Biol Chem. 2005 Apr 15;280(15):15300-6
references.pmid: 15687490
references.citation: EMBO J. 1996 Jun 3;15(11):2893-9
references.pmid: 8654387
references.citation: Biochem J. 1998 Dec 1;336 ( Pt 2):271-82
references.pmid: 9820800
references.citation: Mol Biol Cell. 1995 Jul;6(7):911-27
references.pmid: 7579702
references.citation: Cell. 1988 Feb 12;52(3):329-41
references.pmid: 2964276
references.citation: Cell. 1992 Feb 7;68(3):533-44
references.pmid: 1531449
references.citation: J Control Release. 2005 Jan 20;102(1):247-53
references.pmid: 15653149
references.citation: Science. 1996 Jun 28;272(5270):1935-9
references.pmid: 8658166
references.citation: Proc Natl Acad Sci U S A. 1995 Sep 12;92(19):8655-9
references.pmid: 7567992
references.citation: Nat Cell Biol. 2004 Mar;6(3):189-96
references.pmid: 15039791
references.citation: Circulation. 2003 Oct 21;108(16):1933-8
references.pmid: 14504183
references.citation: J Cell Biol. 1998 Feb 9;140(3):565-75
references.pmid: 9456317
references.citation: Proc Natl Acad Sci U S A. 1998 May 26;95(11):6187-92
references.pmid: 9600939
references.citation: Biochem J. 2004 Jan 1;377(Pt 1):159-69
references.pmid: 14505488
references.citation: Science. 1995 Sep 29;269(5232):1872-5
references.pmid: 7569928
references.citation: Mol Cell. 2001 Mar;7(3):661-71
references.pmid: 11463390
references.citation: Cancer Res. 2007 Sep 15;67(18):8783-90
references.pmid: 17875719
references.citation: J Biol Chem. 2007 Jun 1;282(22):16631-43
references.pmid: 17416589
references.citation: Nat Med. 2003 Mar;9(3):357-62
references.pmid: 12598894
references.citation: J Cell Biol. 1993 Dec;123(6 Pt 1):1373-87
references.pmid: 8253838
references.citation: Vasc Med. 2003;8(1):9-13
references.pmid: 12866606
references.citation: J Biol Chem. 2002 Feb 1;277(5):3371-9
references.pmid: 11724808
references.citation: DNA Cell Biol. 2002 Dec;21(12):895-913
references.pmid: 12573049
references.citation: Pflugers Arch. 2008 Apr;456(1):227-35
references.pmid: 18180951
references.citation: Mol Ther. 2008 Jan;16(1):163-9
references.pmid: 17923843
references.citation: Mol Biol Cell. 2006 Jul;17(7):3197-210
references.pmid: 16672382
references.citation: Proc Natl Acad Sci U S A. 1995 Feb 28;92(5):1327-31
references.pmid: 7877976
references.citation: Cell. 1998 Jun 12;93(6):1021-9
references.pmid: 9635431
references.citation: J Biol Chem. 2008 Apr 25;283(17):11752-62
references.pmid: 18292083
references.citation: J Cell Biol. 1994 Nov;127(3):641-52
references.pmid: 7962049
references.citation: Physiol Genomics. 2007 Oct 22;31(2):159-73
references.pmid: 17684037
references.citation: Hum Gene Ther. 2005 May;16(5):541-50
references.pmid: 15916479
references.citation: J Cell Biol. 1997 Jan 13;136(1):137-54
references.pmid: 9008709
references.citation: Cell. 1992 Sep 4;70(5):715-28
references.pmid: 1516130
references.citation: J Biol Chem. 1998 Feb 6;273(6):3791-7
references.pmid: 9452513
references.citation: Adv Drug Deliv Rev. 2003 Nov 14;55(11):1485-96
references.pmid: 14597142
references.citation: Cell. 1992 Feb 21;68(4):673-82
references.pmid: 1739974
references.citation: Nat Rev Mol Cell Biol. 2001 Oct;2(10):721-30
references.pmid: 11584299
references.citation: Proc Natl Acad Sci U S A. 1997 Apr 1;94(7):3352-6
references.pmid: 9096397
references.citation: Gene Ther. 2003 Mar;10(6):453-8
references.pmid: 12621449