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Wei-Yun Lai
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P2.03 - Biology (ID 162)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Biology
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.03-41 - Identification of Novel Blood-Brain Barrier Penetrating DNA Aptamers (ID 2303)
10:15 - 18:15 | Author(s): Wei-Yun Lai
- Abstract
Background
A significant portion of lung cancer patients develops central nervous system (CNS) metastasis at certain time points in their disease courses. The structure of blood-brain barrier (BBB) strictly regulates brain homeostasis and protects the brain from exogenous damage. At the same time, these features impede effective drug delivery in to CNS, including antibody-based molecular probes. Therefore, detection of small CNS lesions and effective drug delivery across the BBB can be very challenging. Aptamers, also known as chemical antibodies, are small synthetic DNA or RNA oligonucleotides. With its inborn nature of low molecular weight, aptamers may possess better tissue penetrating ability comparing to antibodies. The current study aims to develop BBB-penetrating aptamers for CNS metastatic lung tumor targeting.
Method
In vivo SELEX (Systematic Evolution of Ligands by Exponential enrichment) was used for aptamer identification in the current study. In brief, we established CNS lung cancer mouse models by intra-ventricular inoculation of lung cancer cells. The single-stranded DNA oligonucleotide library was then intraperitoneally injected to the tumor-bearing mice. The mouse was perfused with SELEX buffer and the CNS tissues were carefully isolated. Tissue/tumor-binding oligonucleotide sequences were extracted and amplified by PCR. The procedure was repeated for several rounds and the products of the final SELEX round was subjected for sequencing.
Result
Our data showed that the CNS lung cancer mouse model was nicely established. The growth of tumors was in vivo monitored by IVIS imaging system and confirmed by immunohistochemistry staining. Through in vivo SELEX using the well-established mouse model, a group of potential BBB-penetrating aptamers was identified. By sequence analyses and secondary structure prediction, we further categorized a subset of aptamers that may possess CNS lung tumors targeting ability. Aptamer signals were in vivo captured by IVIS imaging system and was confirmed by confocal microscopy images showing the colocalization of aptamer and lung cancer cell signals.
Conclusion
We have identified BBB-penetrating aptamers that may possess CNS lung tumor targeting ability. The aptamers may serve as guiding molecules for drug delivery and/or probes for molecular imaging. Further studies are required to determine their translational potential.
