Aptamer E07 Against EGFR for Use as an Anti-Tumor Therapeutic

Zane Alami-Nassif
September 3rd, 2013

Aptamer E07 Against EGFR for Use as an Anti-Tumor Therapeutic

            Epidermal growth factor receptor (EGFR) leads to many cancers when over expressed due to a mutation (Zhang et al., 2007). This is because EGFR is a tyrosine kinase receptor that is responsible for binding to epidermal growth factor and initiating a signal transduction cascade that will lead to DNA synthesis and cell proliferation (Oda et al., 2005). If EGFR is constantly activated then uncontrolled cell division will occur leading to malignant tumors.

            The anti-EFGR aptamer, E07, will compete with epidermal growth factor for binding and will thus inhibit the receptor (Li et al., 2011). In figure 1, the sequence of E07 can be observed with the predicted motif that will bind to EFGR. Currently E07 is not as efficient as alternative drugs such as Cetuximab and monoclonal antibodies until a very high dose is used (Avutu 2010). Increasing the efficiency of E07 is a goal that could be pursued in order to bring E07 into viability for treatment against multiple cancers. The theory that avidity effects could increase the efficiency of E07 was tested with limited results. It was hypothesized that nucleic acid would behave in a similar manner to peptides, which obtain supradditve effects when monomers dimerize or multimerize. (Avutu 2010)

Specific Aim 1: The current goal is to better understand the conditions of selection using E07 with two versions of the FT7 primer and positive controls. Whether or not a concentration of aptamer can be maintained after undergoing selection is one focus.

Specific Aim 2: Another focus is to understand the effects of using different buffers during the binding reaction. Buffers to be tested are HBSS without calcium or magnesium, HBSS with calcium and magnesium, PBS and PBS with magnesium.

Figure 1. Predicted secondary structure of Aptamer E01 and Aptamer E07 (Li et al., 2011)
Ordering Information:
Target: Recombinant Human EGFR
Vendor: R&D Systems
Product Catalog Number: 344-ER
Vendor Telephone: (612) 379-2956
Cost: EGFR will be provided by the Altermune lab.

1. Zhang, H., Berezov A., Wang Q., Zhang G., Drebin J., Murali R., Greene M. (2007). ErbB receptors: from oncogenes to targeted cancer therapies. J Clin Invest. 117(8): 2051-2058. 

2. Oda K., Matsuoka Y., Funahashi A., Kitano H. (2005). A comprehensive pathway map of epidermal growth factor signaling. Mol Syst Biol. 1: 2005.0010. 

3. Li N., Nguyen HH., Byrom M., Ellington AD. (2011) Inhibition of Cell Proliferation by an Anti-EGFR Aptamer. PLoS ONE 6(6): e20299.

4. Avutu, V., (2010) Avidity effects of MinE07, an anti-EFGR aptamer, on binding to A431 cells. 

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