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
Ordering Information:
Target: Recombinant Human EGFR
Vendor: R&D Systems
Product Catalog Number: 344-ER
Vendor Website: http://www.rndsystems.com/Products/344-er/
Vendor Telephone: (612) 379-2956
Cost: EGFR will be provided by the
Altermune lab.
References:
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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