Celiac Disease: a model autoimmune disease with gene therapy applications

Londei, Marco; Quaratino, Sonia; Maiuri, Luigi

doi:10.1038/sj.gt.3302041

Cited by 9 publications

(5 citation statements)

References 72 publications

(89 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…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: 93%

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

et al. 2007

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 93%

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

et al. 2007

View full text Add to dashboard Cite

show abstract

“…Finally, gene therapy has been proposed as an intervention in celiac sprue (Londei et al, 2003). Glutenase gene therapy would involve engineering gastrointestinal epithelial progenitors or functionally-specialized cells involved in zymogen secretion (e.g.…”

Section: Lead Optimization For Next-generation Proteasesmentioning

confidence: 99%

Oral Enzyme Therapy for Celiac Sprue

Bethune

Khosla

2012

Methods in Enzymology

View full text Add to dashboard Cite

Celiac sprue is an inflammatory disease of the small intestine caused by dietary gluten and treated by adherence to a lifelong gluten-free diet. The recent identification of immunodominant gluten peptides, the discovery of their cogent properties, and the elucidation of the mechanisms by which they engender immunopathology in genetically-susceptible individuals have advanced our understanding of the molecular pathogenesis of this complex disease, enabling the rational design of new therapeutic strategies. The most clinically advanced of these is oral enzyme therapy, in which enzymes capable of proteolyzing gluten (i.e. glutenases) are delivered to the alimentary tract of a celiac sprue patient to detoxify ingested gluten in situ. In this chapter, we discuss the key challenges for discovery and preclinical development of oral enzyme therapies for celiac sprue. Methods for lead identification, assay development, gram-scale production and formulation, and lead optimization for next-generation proteases are described and critically assessed.

show abstract

“…This peptide could be recognised by Toll-like receptors (TLRs) or other pattern-recognition receptors of intestinal macrophages and dendritic cells, leading to increased synthesis of interleukin (IL)-15 (4,5). IL-15 triggers expression of stress-induced molecules on the epithelium, allows intraepithelial lymphocytes migration and expansion, and protects pathogenic CD4 þ T cells from death (5)(6)(7)(8).…”

Section: Introductionmentioning

confidence: 99%