The blood-brain barrier (BBB) structure is an anatomical marvel in that it is able to effectively separate the brain environment from the circulatory system, preventing damage to the central nervous system by xenobiotics. The structure is made up of microvascular brain endothelial cells (EC) and are highly selective in allowing compounds that are able to traverse the BBB. However, this complicates the delivery of therapeutics from the circulatory system into the brain parenchyma for the treatment of brain-localised tumour cells.
Recently, a study has reported on the high expression of CD98 protein on the BBB EC, generated antibodies against it, and subsequently demonstrated their ability to cross the BBB. Nevertheless, antibodies carry risks of triggering an immune reaction in the brain, potentially damaging healthy tissues. Therefore, an alternative approach must be considered to prevent adverse effects in the central nervous system.
As a synthetic analogue to antibodies, aptamers are short, single-stranded nucleotide sequences that bind to their respective target proteins with high affinity and specificity. They are smaller, highly thermostable, easier to generate compared to antibodies and crucially, immunologically inert.
Hence, this study aims to generate DNA aptamers against the ectodomain of the CD98 protein using the Systemic Evolution of Ligands via Exponential Enrichment (SELEX) method. The aptamers generated will be further characterised in terms of their binding affinity, conformational structure and post-SELEX modifications. Following that, the generated CD98 aptamers will be further evaluated for their BBB transcytosis rates using an in vitro BBB model.
From this preliminary study, it is hoped that further developments of this novel delivery strategy could one day lead to a highly efficient brain tumour treatment modality.