Aptamer Selection against Mammalian Fibroblast Growth Factor 8 b for Early Detection of Prostate Cancer

Aptamer Selection against Mammalian Fibroblast Growth Factor 8 b for Early Detection of Prostate Cancer
Samuel Dugger, Fall 2013

            Despite major advances in oncology over the past few years, cancer still remains one of the most prevalent and deadly diseases affecting mankind today. Even in developed countries like the United States, cancer is one of the top causes of death besides heart disease (Jemal et al, 2011). Although the word “cancer” is used to describe a family of diseases rather than a specific ailment, all cancers are identified by unregulated cell division that results in the formation of tumors that may spread throughout the body (Croce, 2008). Recent studies have suggested that fibroblast growth factors (FGFs) may contribute to the growth of cancers. Overexpressed FGF8b in particular has been linked with prostate cancer (Kwabi-Addo, 2004).

            The main objective of this research is to find an aptamer that could detect FGF8b. Aptamers are oligonucleotides with a high binding affinity for certain molecules, and they have a variety of applications in areas such as drug delivery, diagnostics, therapeutics, developmental biology, and systems and synthetic biology. They have also been proven to be more accurate, more durable, and cheaper to produce than antibodies (which are often used for similar reasons). No custom antibodies have been successfully produced that can locate this target, and aptamers could prove to be the solution.

Figure 1.  This crystallographic image depicts an aptamer (in green) binding to a target molecule (Limson, J 2013).

          Successfully isolating and amplifying an aptamer that can locate FGF8b could help doctors detect prostate cancer in earlier stages and vastly improve patient survival rates. Additionally, this aptamer could be used for targeted drug delivery by carrying cell-destroying chemicals specifically to cancer cells. Shawn Piasecki of the Keatinge-Clay Lab provided last year’s his-tagged FGF8b stock and will continue to do so. Pricing information from this source in particular is unknown, but untagged human FGF8b may be purchased in quantities of 100 ug for $187.16 from US Biological.

Specific Aim: To isolate and amplify an RNA aptamer that binds specifically to FGF8b.

References:

Croce, C. M. (2008). Oncogenes and Cancer. N. Eng. J. Med 358, 502-511.

Jemal, A., Bray, F., Center, M. M., Ferlay, J., Ward, E., Forman, D. (2011). Global cancer statistics. CA Cancer J. Clin. 61(2), 134.

Kwabi-addo ,B., Ozen, M., Ittmann, M. (2004) The role of fibroblast growth factors and their receptors in

prostate cancer. Endocr. Relat. Cancer 11(4), 709-724.

Limson, J., (2013). Aptamers - the right fit for sensors and therapy. Science in Africa.
Link to Target Proposal:  https://docs.google.com/file/d/0B_K32StLhfbjdzlma2plUzdKRjQ/edit?usp=sharing
Link to Progress Report #1:  https://docs.google.com/file/d/0B_K32StLhfbjME9HNHdqaGo5WEk/edit?usp=sharing
Link to Progress Report #2: https://drive.google.com/file/d/0B_K32StLhfbjVDl6WENVTmpFWHM/edit?usp=sharing
Link to Final Report: https://drive.google.com/file/d/0B_K32StLhfbjX29CS01BQm5tWWc/edit?usp=sharing