**6. Aptamers**

Aptamers, single-stranded deoxyribonucleic acid or ribonucleic acid oligonucleotides, are generated by an *in vitro* selection process called SELEX (systematic evolution of ligands by exponential enrichment). They can bind their target molecules with high specificity and selectivity, indicating the probable therapeutic and diagnostic applications for diseases like cancer, inflammatory diseases, etc. [70, 71]. Because aptamers contain some advantages over antibodies and other conventional small-molecule therapeutics, such as high specificity, flexible modification, and low adverse effect, they have been shown as a valuable substi‐ tute to protein antibodies [72]. Moreover, the strategies developed to chemically modify backbone can further improve affinity and bioavailability of aptamers [73]. Higher affinity and specificity could be simultaneously achieved by the genetic-algorithms-based ISM (in silico maturation) [74].

The properties above have paved the way to further studies on introduction of aptamers to preclinical and clinical applications. Based on previous data showing antitumor activity of AS1411, a first-in-class quadruplex DNA aptamer targeting nucleolus, a phase II trial found that AS1411 appears to have dramatic and durable responses in enrolled patients with metastatic renal cell carcinoma, even though about 34% participants have AS1411-related mild adverse events [75]. Malik *et al.* further discovered that AS1411-linked gold nanospheres (AS1411-GNS) could markedly promote superior cellular uptake by cancer cells and increase antiproliferative/cytotoxic effects, with no signs of toxicity [76]. Likewise, other clinical trials on aptmers targeting FIX (Coagulation Factor IX) [77], vWF (von Willebrand factor) [78], and TFPI (tissue factor pathway inhibitor) [79] respectively, all show that aptamers are well tolerated, safe, and represent a new promising target therapy. However, as for some side effects, further clinical investigations are warranted to better define the clinical indications, safety, efficacy, and optimal dosing strategy.
