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01.05.2008 | Basic Research

Gene Delivery to Intestinal Epithelial Cells In vitro and In vivo with Recombinant Adeno-Associated Virus Types 1, 2 and 5

verfasst von: Steven Polyak, Cathryn Mah, Stacy Porvasnik, John-David Herlihy, Martha Campbell-Thompson, Barry J. Byrne, John F. Valentine

Erschienen in: Digestive Diseases and Sciences | Ausgabe 5/2008

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Abstract

Intestinal disorders such as inflammatory bowel disease (IBD) result in chronic illness requiring lifelong therapy. Our aim was to evaluate the efficacy of recombinant adeno-associated virus (AAV) vector-mediated gene delivery to intestinal epithelial cells in vitro and in vivo. Human colon epithelial cell lines and colon biopsies were transduced using AAV pseudotypes 2/1, 2/2, and 2/5 encoding green fluorescence protein (GFP). Mice were administered the same vectors through oral, enema, intraperitoneal (IP) injection and superior mesenteric artery (SMA) injection routes. Tropism and efficiency were determined by microscopy, flow cytometry, immunohistochemistry and PCR. Caco2 cells were more permissive to AAV transduction. Human colon epithelial cells in organ culture were more effectively transduced by AAV2/2. SMA injection provided the most effective means of vector gene transfer to small intestine and colonic epithelial cells in vivo. Transgene detection 80 days post AAV treatment suggests transduction of crypt progenitor cells. This study shows the feasibility of AAV-mediated intestinal gene delivery, applicable for the investigation of IBD pathogenesis and novel therapeutic options, but also revealed the need for further studies to identify more efficient pseudotypes.

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Wirtz S, Neurath MF (2003) Gene transfer approaches for the treatment of inflammatory bowel disease. Gene Ther 10:854–860PubMedCrossRef

Lindsay JO, Sandison A, Cohen P, Brennan FM, Hodgson HJ (2003) IL-10 gene therapy is therapeutic for dextran sodium sulfate-induced murine colitis. Dig Dis Sci 52:363–369

Lindsay J, van Montfrans C, Brennan F, van Deventer S, Drillenburg P, Hodgson H, te Velde A, Sol Rodriguez Pena M (2002) IL-10 gene therapy prevents TNBS-induced colitis. Gene Ther 9:1715–1721PubMedCrossRef

Jobin C, Panja A, Hellerbrand C, Iimuro Y, Didonato J, Brenner DA, Sartor RB (1998) Inhibition of proinflammatory molecule production by adenovirus-mediated expression of a nuclear factor kappa B super-repressor in human intestinal epithelial cells. J Immunol 160:410–418PubMed

Vermeire S, Rutgeerts P (2005) Current status of genetics research in inflammatory bowel disease. Genes Immun 6:637–645PubMed

Westbrook CA, Chmura SJ, Arenas RB, Kim SY, Otto G (1994) Human APC gene expression in rodent colonic epithelium in vivo using liposomal gene delivery. Hum Mol Genet 3:2005–2010PubMedCrossRef

Li M, Lonial H, Citarella R, Lindh D, Colina L, Kramer R (1996) Tumor inhibitory activity of anti-ras ribozymes delivered by retroviral gene transfer. Cancer Gene Ther 3:221–229PubMed

Seppen J, Barry SC, Klinkspoor JH, Katen LJ, Lee SP, Garcia JV, Osborne WR (2000) Apical gene transfer into quiescent human and canine polarized intestinal epithelial cells by lentivirus vectors. J Virol 74:7642–7645PubMedCrossRef

Varghese S, Rabkin SD (2002) Oncolytic herpes simplex virus vectors for cancer virotherapy. Cancer Gene Ther 9:967–978PubMedCrossRef

10.

Foreman PK, Wainwright MJ, Alicke B, Kovesdi I, Wickham TJ, Smith JG, Meier-Davis S, Fix JA, Daddona P, Gardner P, Huang MT (1998) Adenovirus-mediated transduction of intestinal cells in vivo. Hum Gene Ther 9:1313–1321PubMedCrossRef

11.

Wirtz S, Becker C, Blumberg R, Galle PR, Neurath MF (2002) Treatment of T cell-dependent experimental colitis in SCID mice by local administration of an adenovirus expressing IL-18 antisense mRNA. J Immunol 168:411–420PubMed

12.

Hackett NR, Kaminsky SM, Sondhi D, Crystal RG (2000) Antivector and antitransgene host responses in gene therapy. Curr Opin Mol Ther 2:376–382PubMed

13.

Hoggan MD, Blacklow NR, Rowe WP (1966) Studies of small DNA viruses found in various adenovirus preparations: physical, biological, and immunological characteristics. Proc Natl Acad Sci USA 55:1467–1474PubMedCrossRef

14.

Berns KI, Hauswirth WW (1979) Adeno-associated viruses. Adv Virus Res 25:407–449PubMed

15.

Samulski RJ, Berns KI, Tan M, Muzyczka N (1982) Cloning of adeno-associated virus into pBR322: rescue of intact virus from the recombinant plasmid in human cells. Proc Natl Acad Sci USA 79:2077–2081PubMedCrossRef

16.

Zhou X, Muzyczka N (1998) In vitro packaging of adeno-associated virus DNA. J Virol 72:3241–3247PubMed

17.

Monahan PE, Samulski RJ (2000) Adeno-associated virus vectors for gene therapy: more pros than cons? Mol Med Today 6:433–440PubMedCrossRef

18.

Stilwell JL, Samulski RJ (2003) Adeno-associated virus vectors for therapeutic gene transfer. Biotechniques 34:148–159PubMed

19.

Zaiss AK, Liu Q, Bowen GP, Wong NC, Bartlett JS, Muruve DA (2002) Differential activation of innate immune responses by adenovirus and adeno-associated virus vectors. J Virol 76:4580–4590PubMedCrossRef

20.

During MJ, Xu R, Young D, Kaplitt MG, Sherwin RS, Leone P (1998) Peroral gene therapy of lactose intolerance using an adeno-associated virus vector. Nat Med 4:1131–1135PubMedCrossRef

21.

Shao G, Greathouse K, Huang Q, Wang C, Sferra T (2006) Gene transfer to the gastrointestinal tract after peroral administration of recombinant adeno-associated virus type 2 vectors. J Pediatr Gastroenterol Nutr 43:168–179PubMedCrossRef

22.

Zolotukhin S, Potter M, Hauswirth WW, Guy J, Muzyczka N (1996) A “humanized” green fluorescent protein cDNA adapted for high-level expression in mammalian cells. J Virol 70:4646–4654PubMed

23.

Zolotukhin S, Byrne BJ, Mason E, Zolotukhin I, Potter M, Chesnut K, Summerford C, Samulsk RJ, Muzyczka N (1999) Recombinant adeno-associated virus purification using novel methods improves infectious titer and yield. Gene Ther 6:973–985PubMedCrossRef

24.

Zolotukhin S, Potter M, Zolotukhin I., Sakai Y, Loiler S, Fraites TJ Jr, Chiodo VA, Phillipsberg T, Muzyczka N, Hauswirth WW, Flotte TR, Byrne BJ, Snyder RO (2002) Production and purification of serotype 1, 2, and 5 recombinant adeno-associated viral vectors. Methods 28:158–167PubMedCrossRef

25.

Ferrari FK, Samulski T, Shenk T, Samulski RJ (1996) Second-strand synthesis is a rate-limiting step for efficient transduction by recombinant adeno-associated virus vectors. J Virol 70:3227–3234PubMed

26.

Rochlitz CF (2000) Gene therapy of cancer. Drugs Today 36:619–629PubMed

27.

Wagner JA, Nepomuceno IB, Messner AH, Moran ML, Batson EP, Dimiceli S, Brown BW, Desch JK, Norbash AM, Conrad CK, Guggino WB, Flotte TR, Wine JJ, Carter BJ, Reynolds TC, Moss RB, Gardner P (2002) A phase II, double-blind, randomized, placebo-controlled clinical trial of tgAAVCF using maxillary sinus delivery in patients with cystic fibrosis with antrostomies. Hum Gene Ther 3:1349–1359CrossRef

28.

Leone P, Janson CG, Bilaniuk L, Wang Z, Sorgi F, Huang L, Matalon R, Kaul R, Zeng Z, Freese A, McPhee SW, Mee E, During MJ (2000) Aspartoacylase gene transfer to the mammalian central nervous system with therapeutic implications for Canavan disease. Ann Neurol 48:27–38PubMedCrossRef

29.

Kay MA, Manno CS, Ragni MV, Larson PJ, Couto LB, McClelland A, Glader B, Chew AJ, Tai SJ, Herzog RW, Arruda V, Johnson F, Scallan C, Skarsgard E, Flake AW, High KA (2000) Evidence for gene transfer and expression of factor IX in haemophilia B patients treated with an AAV vector. Nat Genet 24:257–261PubMedCrossRef

30.

Londei M, Quaratino S, Maiuri L (2003) Celiac disease: a model autoimmune disease with gene therapy applications. Gene Ther 10:835–843PubMedCrossRef

31.

Prieto J, Herraiz M, Sangro B, Qian C, Mazzolini G, Melero I, Ruiz J (2003) The promise of gene therapy in gastrointestinal and liver diseases. Gut 52(S2):49–54

32.

Tang SC, Sambanis A, Sibley E (2005) Proteosome modulating agents induce rAAV2-mediated transgene expression in human intestinal epithelial cells. Biochem Biophys Res Commun 31:1392–1400CrossRef

33.

Walters RW, Pilewski JM, Chiorini JA, Zabner J (2002) Secreted and transmembrane mucins inhibit gene transfer with AAV4 more efficiently than AAV5. J Biol Chem 277:23709–23713PubMedCrossRef

34.

Summerford C, Samulski RJ (1998) Membrane-associated heparan sulfate proteoglycan is a receptor for adeno-associated virus type 2 virions. J Virol 72:1438–1445PubMed

35.

McCarty DM, Fu H, Monahan PE, Toulson CE, Naik P, Samulski RJ (2003) Adeno-associated virus terminal repeat (TR) mutant generates self-complementary vectors to overcome the rate-limiting step to transduction in vivo. Gene Ther 10:2112–2118PubMedCrossRef

36.

Kessler PD, Podsakoff GM, Chen X, McQuiston SA, Colosi PC, Matelis LA, Kurtzman GJ, Byrne BJ (1996) Gene delivery to skeletal muscle results in sustained expression and systemic delivery of a therapeutic protein. Proc Natl Acad Sci USA 93:14082–14087PubMedCrossRef

37.

Song S, Embury J, Laipis PJ, Berns KI, Crawford JM, Flotte TR (2001) Stable therapeutic serum levels of human alpha-1 antitrypsin (AAT) after portal vein injection of recombinant adeno-associated virus (rAAV) vectors. Gene Ther 8:1299–1306PubMedCrossRef

38.

Bals R, Xiao W, Sang N, Weiner D, Meegalla R, Wilson J (1999) Transduction of well-differentiated airway epithelium by recombinant adeno-associated virus is limited by vector entry. J Virol 73:6085–6088PubMed

39.

Sandberg JW, Lau C, Jacomino M, Finegold M, Henning SJ (1994) Improving access to intestinal stem cells as a step toward intestinal gene transfer. Hum Gene Ther 5:323–329PubMedCrossRef

40.

Pickles RJ, Fahrner JA, Petrella JM, Boucher RC, Bergelson JM (2000) Retargeting the coxsackievirus and adenovirus receptor to the apical surface of polarized epithelial cells reveals the glycocalyx as a barrier to adenovirus-mediated gene transfer. J Virol 74:6050–6057PubMedCrossRef

41.

Xie X, Forsmark CE, Lau JY (2000) Effect of bile and pancreatic juice on adenoviral-mediated gene delivery: implications on the feasibility of gene delivery through ERCP. Dig Dis Sci 45:230–236PubMedCrossRef

42.

Seiler MP, Miller AD, Zabner J, Halbert CL (2006) Adeno-associated virus types 5 and 6 use distinct receptors for cell entry. Hum Gene Ther 17:10–19PubMedCrossRef

43.

Sferra TJ, McNeely D, Johnson PR (1997) Gene transfer to the intestinal tract: a new approach using selective injection of the superior mesenteric artery. Hum Gene Ther 8:681–687PubMedCrossRef

44.

Gao GP, Alvira MR, Wang L, Calcedo R, Johnston J, Wilson JM (2002) Novel adeno-associated viruses from rhesus monkeys as vectors for human gene therapy. Proc Natl Acad Sci USA 99:11854–11859PubMedCrossRef

Titel: Gene Delivery to Intestinal Epithelial Cells In vitro and In vivo with Recombinant Adeno-Associated Virus Types 1, 2 and 5
verfasst von: Steven Polyak
Cathryn Mah
Stacy Porvasnik
John-David Herlihy
Martha Campbell-Thompson
Barry J. Byrne
John F. Valentine
Publikationsdatum: 01.05.2008
Verlag: Springer US
Erschienen in: Digestive Diseases and Sciences / Ausgabe 5/2008
Print ISSN: 0163-2116
Elektronische ISSN: 1573-2568
DOI: https://doi.org/10.1007/s10620-007-9991-1

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