The Brain's New Hero: Nucleic Acid Aptamer Selection Against Beta-Glucuronidase

Nucleic Acid Aptamer Selection Against Beta-Glucuronidase
Ellen Airhart
Nucleic Acid Pool: N71 RNA Pool
Target: Beta-Glucuronidase

Microglia are a type of glial cell found in the central nervous system. There, they act as the first line of defense of the nervous system.  Stimulation of microglia is a signal of infectious, inflammatory, and degenerative illnesses of the CNS. This inflammation could be indicative of many diseases, such as Alzheimer’s, dementia, and other neurodegenerative conditions. Studies have shown that there is a rise in the release of β- glucuronidase, or GUS, by stimulated microglia into the extracellular space at an area of neuroinflammation. GUS is involved in the hydrolysis of glycosaminoglycans on the cell surface and the degeneration of the extracellular matrix. Therefore, GUS might be a biomarker for continuing neurodegeneration induced by neuroinflammation (Antunes, Doorduin, Haisma, Elsinga, Waarde, Willemson, Dierckx & Vries, 2012).
An aptamer, or an olglionucleic acid or peptide molecule that have been carefully selected to bind to its target in a similar way to an antibody (Pai, Roberts & Ellington, 2008), has not been discovered for Beta-Glucuronidase. If an aptamer was developed to bind to GUS it could be used as a biomarker to assist in diagnosing neurodegenerative diseases.
Primary Specific Aim: Identifying an aptamer that binds to GUS-His

Figure 1 illustrates the active sites Glu451, Tyr504, Glu540, and Asn450. This high number of active sites increases the chance that there is an aptamer for this target.
Secondary Specific Aim: Use this aptamer as a biomarker for neurodegenerative inflammation

Target Order Information
Vendor: Ellington Lab
Vendor Website:
Central Lab Telephone:  512-471-6445
Office Manager:  512-232-3426
Cost per Unit: $0
            Cost per Round: $0
Antunes, I., Doorduin, J., Haisma, H., Elsinga, P., Waarde, A., Willemson, A., Dierckx, R., & Vries, E. (2012). F-feanga for pet of β-glucuronidase activity in neuroinflammation. Journal of Nuclear Medicine, 53(3), 451-458.
Lawson L J, Perry V H, Gordon S (1992). "Turnover of resident microglia in the normal adult mouse brain". Neuroscience 48: 405–415.

Pai, S., Roberts , A., & Ellington , A. (2008). Aptamer amplification: divide and signal. Expert Opinion on Medical Diagnostics, 2(12), 1333-1346. doi: 10.1517/17530050802562016
Roffler, S., Wu, C., Schechinger, W., Chen, K., & Prijovic, Z. (2009). Human beta-glucuronidase mutants with elevated enzymatic activity under physiological conditions and methods for identifying as such. 
First Target Proposal
First Progress Report
Second Progress Report
Final Progress Report

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