Rational design of aptamer-based biosensors

点击翻译按钮获取中文摘要

Given increasing concerns about infectious diseases, bioterrorism agents, and environmental contaminants, there is an urgent need to develop the tools for rapid and accurate detection and identification of a target at low concentrations.  Biosensors are analytical devices that transduce a biological recognition event into a measurable response.  In order to rationally design biosensors, we must find the correct recognition element for the target, understand the mechanism of the recognition event, and develop the strategy for transducing that event into a measurable signal.  Antibodies are the current standard in biosensing, due to their strong and selective binding to many targets. However, some have limitations with regards to stability and ease of preparation.  The proposed research program seeks to investigate the use of short stretches of DNA or RNA, known as aptamers, as the building blocks for new biosensors.  Aptamers are synthetic pieces of DNA or RNA that act like antibodies, binding tightly to a specific target, but have the added advantage of being easier to prepare and demonstrating improved stability over their antibody counterparts.  Aptamers have been developed to bind to a host of targets that can be important analytes for biosensors: toxins, cancer markers, proteins, and even viruses.  Now the challenge is to design the biosensor architecture that will take the recognition event of aptamer binding and translate it into a signal.  Before we can do that in a rational manner we need a better understanding of how aptamers bind to their targets.  Our first goal is to design new probes to study and understand the structural changes that take place when an aptamer binds to its target, as the change in the shape of the aptamer is thought to be the key to the binding event.  With this information we can then proceed to our second goal, to design and implement architectures that can transduce this change in aptamer structure into a measurable signal.  In the long term, our systematic approach to the study of aptamer structure and the design of new aptamer-based biosensors could enable important advances in sensing for a range of milieus, from medical diagnostics to environmental monitoring.