Development of an RNA aptamer to PD173955N through SELEX

Mehanovic, Samir
Major Professor
Marit Nilsen-Hamilton
Amy Andreotti
W. A. Miller
Committee Member
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Biochemistry, Biophysics and Molecular Biology

With all the technology available to us, the causes of cancers are still puzzling researchers all over the world. Everyday different approaches are being tested to help cure various cancers. With the development of molecular biology, we are able to understand cancer more at molecular level, which helps us look at different methods to treat cancer patients.;The molecular basis for leukemia cancers are understood to a level where we are able to design treatments that specifically target proteins responsible for the disease. One of those proteins is the Bcr-Abl tyrosine kinase which is mostly responsible for chronic myelogenous leukemia. PD173955 is a drug that is capable of inhibiting Bcr-Abl tyrosine kinase more potently than any other chemotherapeutic drug reported drug. The problem with PD173955 and a very large number of other drugs is their limited solubility in aqueous environments which makes them less desirable for medical applications.;Aptamers are newly developed reagents and their utilization in medicinal applications is so far very limited. However their characteristics make them perfect tools to help solve problems associated with PD173955. Here we report a successful selection of the RNA aptamer that is capable of binding PD173955 with a dissociation constant of 1-2 muM using SELEX. The data obtained with selected aptamer suggests that the aptamer could be used to protect PD173955 from aqueous environment. The selection process of the RNA aptamer will be described in detail. The selected aptamer has been reduced to its minimal binding domain without loss of affinity.