Aptamer Technology for Diabetes and Co-Morbidities

Abstract

Given that the number of people who are diagnosed with diabetes continues to rise at an alarming rate, there is a pressing need for therapeutic interventions that are either more efficient or potentially curative. Furthermore, co-morbidities such as kidney failure, thrombosis, thyroid dysfunction, Alzheimer's disease, and an increased risk of severe illness from common viral and bacterial infections are more likely to occur in people who have type 2 diabetes. The advancement of nanotechnology may lead to the diagnostics and therapies that could improve the survival and quality of life of patients with diabetes. Aptamers are oligonucleotides that have the ability to bind to a particular target with a high degree of specificity as well as affinity.Systematic evolution of ligands by exponential enrichment (SELEX) is an in vitro evolution method that is responsible for the generation of aptamers. It has been shown that aptamers may function as medicines, diagnostics, theranostics, targeted delivery vehicles, responsive materials and more. This work examines the application of aptamers to diabetes and related comorbidities. The selection and preliminary characterization of aptamers able to interact with Islet amyloid polypeptide (IAPP), a potential causative factor in the development of type II diabetes, are described. An aptamer-based diagnostic for the acute kidney failure biomarker neutrophil gelatinase lipocalin protein is also developed. An aptamer-modified janus nanoparticle system is investigated as a potential theragnostic for thrombosis that could combine photothermal therapy and magnetic resonance imaging. Finally, aptamers for the spike protein component 2 of SARS-CoV2 and a database for aptamer selection experiments are briefly described.iii Preface: This introduction provides bibliographical information for each article that is included into this thesis, along with an explanation of whether the piece is replicated in its whole or in part. The use of content protected by intellectual property laws is also recognised here. If a chapter in this thesis is based on a publication, please reference the article that is relevant to that chapter when you are referring to material from this thesis. Due to the fact that this thesis is written in the style of an integrated thesis, it is essential to take into consideration the possibility that part of the information presented in the introductions, as well as the materials and methods sections, will be repeated.Chapter 1 consists of a brief introduction of necessary background for research conducted in this thesis.Chapter 2 consists of a pretreatment method used for the preparation of monomeric islet amyloid polypeptide. The manuscript was reproduced and edited for formatting and clarity of presentation.Chapter 3 consists of the Systematic evolution of ligands by exponential enrichment for islet amyloid polypeptide target.Chapter 4 consists of diagnostic lateral flow-based development for neutrophil gelatinase lipocalin protein, an acute kidney failure biomarker.Chapt...