title: What's Next for Gastrointestinal Disorders: No Needles?
abstract: A myriad of pathologies affect the gastrointestinal tract, citing this affected area as a significant target for therapeutic intervention. One group of therapeutic agents, antisense and oligonucleotides and small interfering RNAs, offer a promising platform for treating a wide variety of diseases ranging from cancer to auto-immune diseases. Current delivery methods are carried out either systemically or locally into diseased areas, both of which involve needles. The challenge in orally administering this type of treatment lies in the complications that arise due to the vast environmental extremes found within the gastrointestinal tract, owing to the fact that, as the drug travels down the gastrointestinal tract, it is subjected to pH changes and interactions with bacteria and a variety of digestive and protective enzymes including proteases, DNAses, and RNAses. Overcoming these challenges to allow the practical application of these drugs is a priority that has invoked a multitude of research in the chemical, biological, and material sciences. In this review, we will address common gastrointestinal pathologies, the barriers to oral-based therapies and antisense-interfering technologies, the approaches that have already been applied for their delivery, and the current status of antisense drug therapy clinical trials for gastrointestinal-related disorders.
authors.affiliation: Biomedical Technology and Cell Therapy Research Laboratory, Departments of Biomedical Engineering and Physiology Artificial Cells and Organs Research Center, Faculty of Medicine, McGill University, 3775 University Street, Montreal, Quebec, Canada.
authors.forename: Aleksandra M
authors.initials: AM
authors.lastname: Urbanska
authors.affiliation: Synthetic Neurobiology Group, Massachusetts Institute of Technology Media Lab and McGovern Institute, Departments of Biological Engineering and Brain and Cognitive Sciences, Cambridge, MA 02139, USA.
authors.forename: Emmanouil D
authors.initials: ED
authors.lastname: Karagiannis
authors.affiliation: Division of Digestive and Liver Diseases, Columbia University College of Physicians and Surgeons, New York, NY 10032-3802, USA.
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Au
authors.affiliation: Biomedical Technology and Cell Therapy Research Laboratory, Departments of Biomedical Engineering and Physiology Artificial Cells and Organs Research Center, Faculty of Medicine, McGill University, 3775 University Street, Montreal, Quebec, Canada.
authors.forename: Si Yuan
authors.initials: SY
authors.lastname: Dai
authors.affiliation: Bioengineering Research Group, Nanotechnology and Advanced Materials Department, Materials and Energy Research Center (MERC), P.O. Box 14155-4777, Tehran, Iran. Electronic address: mozafari.masoud@gmail.com.
authors.forename: Masoud
authors.initials: M
authors.lastname: Mozafari
authors.affiliation: Biomedical Technology and Cell Therapy Research Laboratory, Departments of Biomedical Engineering and Physiology Artificial Cells and Organs Research Center, Faculty of Medicine, McGill University, 3775 University Street, Montreal, Quebec, Canada.
authors.forename: Satya
authors.initials: S
authors.lastname: Prakash
mesh_terms: D000818:Animals; D016503:Drug Delivery Systems; D005767:Gastrointestinal Diseases / Q000473:pathology / Q000628:therapy*; D041981:Gastrointestinal Tract / Q000378:metabolism / Q000473:pathology; D018014:Gene Transfer Techniques; D006801:Humans; D009339:Needles; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use
chemical_list: D016376:Oligonucleotides, Antisense; D034741:RNA, Small Interfering
keywords: Antisense; Gastrointestinal tract; Oligonucleotides; Oral delivery; Small interfering RNAs