Gene transfer approaches for the treatment of inflammatory bowel disease

Wirtz, Stefan; Neurath, Markus F.

doi:10.1038/sj.gt.3302013

Cited by 36 publications

(29 citation statements)

References 104 publications

(105 reference statements)

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“…The luminal gastrointestinal tract, as a target for gene transfer, could provide a therapeutic strategy and aid research to help decipher the pathogenesis of a variety of epitheliumderived diseases such as IBDs, hemochromatosis and intestinal cancers. The potential for the application of gene therapy in diseases related to the gastrointestinal tract-especially the colon-has been the subject of several recent reviews [1,30,31]. The results of this project demonstrate that colonic epithelial cells are susceptible to in vitro and ex vivo transduction with AAV pseudotypes 2/1, 2/1 and 2/5.…”

Section: Discussionmentioning

confidence: 94%

“…Although in its infancy, transgene products such as proteins and antisense RNA that intently down-regulate pathogenic responses or induce protective immune responses are becoming a reality [1]. The difficulty in treating chronic inflammatory intestinal disorders such inflammatory bowel disease (IBD) warrant the investigation of biological therapy within the gastrointestinal tract via localized gene delivery and endogenous protein expression [2][3][4].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2007

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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. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript 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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Section: Discussionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

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

et al. 2007

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“…IL-10 gene therapy has had a significant positive effect as treatment in IBD model mice [19,20]. However, phase III clinical trials using recombinant IL-10 administered subcutaneously have not shown a beneficial effect in IBD patients [21,22], possibly due to decreased bioavailability of IL-10 in the intestinal mucosa.…”

mentioning

confidence: 99%

Function of the glycosyltransferase GnT-V in colitis

Nonaka

2015

J Gastroenterol

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“…Inability of the immune system to control the response leads to the development of an inflammatory disease. Several therapeutic strategies are available for the treatment of inflammatory disease (4,5). In this review, we discuss the role of immune modulation using targets ranging from antigen-presenting cells to activated T cells, macrophages, and B cells for the treatment of inflammatory diseases.…”

Section: Introductionmentioning

confidence: 99%

Translational Nano-Medicines: Targeted Therapeutic Delivery for Cancer and Inflammatory Diseases

Talekar

Trần

Amiji

2015

AAPS J

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Abstract. With the advent of novel and personalized therapeutic approaches for cancer and inflammatory diseases, there is a growing demand for designing delivery systems that circumvent some of the limitation with the current therapeutic strategies. Nanoparticle-based delivery of drugs has provided means of overcoming some of these limitations by ensuring the drug payload is directed to the disease site and insuring reduced off-target activity. This review highlights the challenges posed by the solid tumor microenvironment and the systemic limitations for effective chemotherapy. It then assesses the basis of nanoparticle-based targeting to the tumor tissues, which helps to overcome some of the microenvironmental and systemic limitations to therapy. We have extensively focused on some of the tumor multidrug resistance mechanisms (e.g., hypoxia and aerobic glycolysis) that contribute to the development of multidrug resistance and how targeted nano-approaches can be adopted to overcome drug resistance. Finally, we assess the combinatorial approach and how this platform has been used to develop multifunctional delivery systems for cancer therapy. The review article also focuses on inflammatory diseases, the biological therapies available for its treatment, and the concept of macrophage repolarization for the treatment of inflammatory diseases.

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Gene transfer approaches for the treatment of inflammatory bowel disease

Cited by 36 publications

References 104 publications

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

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

Function of the glycosyltransferase GnT-V in colitis

Translational Nano-Medicines: Targeted Therapeutic Delivery for Cancer and Inflammatory Diseases

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