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:
https://www.ellingtonlab.org
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 ProposalFirst Progress Report
Second Progress Report
Final Progress Report
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