Aptamers are single-stranded RNA or DNA oligonucleotides, which could be screened and synthesized for specific target (including any cell type), using systematic evolution of ligands by exponential enrichment (SELEX) technology. Aptamers are known for more than two decades and have been used successfully for molecular diagnostics, targeted therapy, biomarkers discovery, as biosensensors for cell labeling and other applications. Cell-SELEX technology was used for aptamer-based isolation of cells in cancer and stem cell research (reviewed here). In cell therapy, aptamers could be used for (1) cell tracking (reviewed here) and (2) cell isolation. I’d like to focus on application of aptamers for cell isolation.
In research, aptamers have been used for isolation of mesenchymal stromal cells, embryonic stem cells and immune cells. However, to my knowledge, there are no reports on use of aptamers in cell therapy clinical trials (for cell tracking or cell isolation purposes). I was able to find only one research paper, which experimentally assesses therapeutic value of aptamer-isolated cells.
Aptamer-based cell isolation is very similar to antibodies. Compared to antibodies, multiple authors are indicating the following advantages of aptamers:
- small size allows wider bioavailability
- lack of immunogenicity
- easy chemical synthesis and scale-out manufacturing
- easy to modify
- high stability
- possibility of decoupling from the cells.
Aptamers and antibodies have comparable specificity and result in similar cell yield after isolation. Potential disadvantages of aptamers in cell therapy are the following:
- few clones should be tested for specificity
- non-specific binding with other types of cells, optimization required
- relatively low cell yield after decoupling
- not qualified (approved) for clinical cell isolation
- unknown safety (not rigorously tested for biocompatibility).
Study from S. Korea, published last year in PLoS ONE, is the most rigorous (as of today) pre-clinical assessment of aptamers for cell isolation. I’d highly recommend to read this study if you’re interested in cell isolation techniques.
The concept of using aptamers in clinical cell manufacturing looks very attractive to me. I’m not sure why this approach is not gaining momentum in cell therapy. If you ever have worked with aptamers and read on this topic, please share your thoughts on its potential application in cell therapy. Also, if you know any manufacturer of clinical-grade aptamers, please let me know.