The treatment of brain disorders is greatly hindered by the presence of the blood-brain barrier, which restricts the overwhelming majority of small molecules from entering the brain. A novel approach by which to overcome this barrier is to target receptor mediated transport mechanisms present on the endothelial cell membranes. Therefore, we fused an aptamer that binds to epithelial cell adhesion molecule-expressing cancer cells to an aptamer targeting the transferrin receptor. This generated a proof of concept bifunctional aptamer that can overcome the blood-brain barrier and potentially specifically target brain disorders. The initial fusion of the two sequences enhanced the binding affinity of both aptamers while maintaining specificity. Additionally, mutations were introduced into both binding loops to determine their effect on aptamer specificity. The ability of the aptamer to transcytose the blood-brain barrier was then confirmed in vivo following a 1 nmol injection. This study has shown that through the fusion of two aptamer sequences, a bifunctional aptamer can be generated that has the potential to be developed for the specific treatment of brain disorders.
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Article Synopsis
- Aptasensors detect biomolecules by transforming the binding of specific target molecules with aptamers into measurable signals, helping in rapid biomolecule identification.
- The study compares different crosslinkers used for immobilizing aptamers, focusing on one homo-bifunctional and three hetero-bifunctional types, specifically for attaching the Ebola soluble Glycoprotein (sGP) binding DNA aptamer to surfaces.
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