Audri Dugger's CIAP Aptamer Project (2015)

Introduction

Over 700,000 Americans continuously suffer with the painful symptoms of Crohn’s Disease. Crohn’s disease is an inflammatory bowel disease (IBD) that causes the lining of the small and large intestines to inflame. Harmless bacteria that line the intestines are mistaken as foreign, harmful bacteria. The body reacts to eliminate all the bacteria, eliciting the inflammatory response. The inflammation leads to fatigue, major weight loss, malnutrition, diarrhea and serve abdominal inflammation.2 Although the cause of Crohn’s disease is unknown, individuals affected have been found to contain higher amounts of tumor necrosis factor alpha (TNF). Tumor necrosis factor alpha is a messenger protein that plays vital roles in the body’s immune response to foreign objects, especially tumors. TNF enhances inflammation and increases the production of cells used in an inflammatory response.3 The development and continuance of Crohn’s disease is thought to be caused by the presence of excess amounts of tumor necrosis factor alpha.

Calf-Intestinal Alkaline Phosphatase , commonly known as CIAP, reduces Lipopolysaccharide (LPS)-mediated inflammatory response, primarily tumor necrosis factor alpha. In a study conducted by the Journal of Pharmacology, the presence of CIAP decreased the amount of tumor necrosis in mice and pigs by 98%. 4 Based on this discovery, not only can CIAP lessen the painful symptoms of Crohn’s Disease by decreasing the inflammation of the GI tract, but an aptamer, a specific single stranded RNA or DNA sequence, bonded to CIAP can aid in the diagnosis and therapeutics/treatment.

The aptamer for Crohn’s disease has two possible functions. First of all, the aptamer could be tagged with a specific type of fluorescent tail. The CIAP would bind to the intestinal wall where the inflammation is greatest, and will provide relief to the patient as well as allowing doctors to locate the exact location of the disease. Over time, if the disease spreads to cover more of the intestines, the fluorescent tail would identify the growth patterns, helping doctors to better understand Crohn’s Disease and how it develops. Since Crohn’s disease has been shown to have some genetic linkage, CIAP with the aptamer and fluorescent tail could provide early detection and aid with decreasing symptoms and growth early on in infants. Secondly, the CIAP reporter molecule and the specific aptamer could be bonded with antibiotics or other medicines that could help to reduce inflammation, and pain as well as ulcers that can form in the intestines. With this aptamer, patients suffering with Crohn’s disease will be provided great relief from the painful symptoms they suffer from every day.

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Citations

1.) Comparison of the Appearance of Normal, Crohn’s, and Ulcerative Colitis Mucosa Gross(top);Histological(center);Endoscopic (bottom). Digital image. Gastroenterology & Hepatology: Crohns's Disease. Johns Hopkins Medicine, n.d. Web

2.) "Crohn's Disease." Disease and Conditions. Mayo Clinic, n.d.

3.) "Crohn's & Colitis." CCFA: What Is Crohn's Disease. Crohn's & Colitis Foundation of America, n.d.

4.) Beumer, C., Wulferink, M., Raaben, W., Fiechter, D., Brands, R., and Seinen, W. (2003). Calf Intestinal Alkaline Phosphatase, a Novel Therapeutic Drug for Lipopolysaccharide (LPS)-Mediated Diseases, Attenuates LPS Toxicity in Mice and Piglets. J Pharmacol Exp Ther 307, 737–744.

5.) Huynh, Vincent. "Aptamer Project Site - 10% APS for Everyone." : Therapuetic RNA Aptamers against Calf Intestinal Alkaline Phosphatase. N.p., n.d.

6.) Jacquel, Arnaud, and Patrick Auberger. CIAPs and XIAP Reduce RIPKs to Silence. Digital image. Phagoctes, Granulocytes & Myelopoiesis. American Society of Hematology, n.d. Web.

7.) Lou, K-J. Conformational Change upon Binding to Target. Digital image. Imaging with Aptamers. Nature Middle East, n.d. Web.

8.) "Phosphatase, Alkaline." - Worthington Enzyme Manual. Worthington Biochemical Corperations, n.d.

9.) Zhou, Wenhu, Pro- Jung Jimmy Huang, Jinsong Ding, and Juewen Liu. Aptamer-based Biosensors for Biomedical Diagnostics. Digital image. Publishing; Journals, Books and Databases. Analyst, n.d. Web.