Aptamer-based diagnostic and therapeutic approaches in animals: Current potential and challenges

Abstract

Fast and precise diagnosis of infectious and non-infectious animal diseases and their targeted treatments are of utmost importance for their clinical management. The existing biochemical, serological and molecular methods of disease diagnosis need improvement in their specificity, sensitivity and cost and, are generally not amenable for being used as points-of-care (POC) device. Further, with dramatic changes in environment and farm management practices, one should also arm ourselves and prepare for emerging and re-emerging animal diseases such as cancer, prion diseases, COVID-19, influenza etc. Aptamer – oligonucleotide or short peptides that can specifically bind to target molecules – have increasingly become popular in developing biosensors for sensitive detection of analytes, pathogens (bacteria, virus, fungus, prions), drug residues, toxins and, cancerous cells. They have also been proven successful in the cellular delivery of drugs and targeted therapy of infectious diseases and physiological disorders. However, the in vivo application of aptamer-mediated biosensing and therapy in animals has been limited. This paper reviews the existing reports on the application of aptamer-based biosensors and targeted therapy in animals. It also dissects the various modifications to aptamers that were found to be successful in in vivo application of the aptamers in diagnostics and therapeutics. Finally, it also highlights major challenges and future directions in the application of aptamers in the field of veterinary medicine.

Identification of G-quadruplex anti-Interleukin-2 aptamer with high specificity through SELEX stringency

“…According to a study by Low et al., the aptamer production cost is 10–50 times lower than the antibody. Therefore, the future perspective is more toward the use of aptamers for diagnosis or therapy in different diseases [ 9 ].…”

“…The necessity of new laboratory methods for identifying ligands with high affinity has led to the creation of aptamers for new therapeutic and diagnostic approaches [ 9 , 10 ]. Aptamers are 3D (3-dimensional)-structured and in vitro-chemically synthesized of short oligonucleotides of ssDNA or ssRNA, which could bind against many targets such as ions, antibiotics, and amino acids, as well as large protein complexes, enzymes, antibodies, and cell surface receptors with high affinity and specificity [ 11 , 12 ].…”

Therapeutic Potential of Aptamer–Protein Interactions

“…Thousands of aptamers have been developed over the years against various types of targets, including coagulation factors, growth factors, hormones, antibodies, neuropeptides, small metal ions, viruses, bacteria, whole living cells, toxins, proteins, and biomarkers, and even targets within live animals . In addition, aptamers can be selected toward toxic and poorly immunogenic targets, whereas antibodies produced in vivo cannot be generated to such targets . Indeed, a remarkable aspect of aptamers is that, in principle, they can be generated for selective binding to virtually any target …”

“…Flexible unbound regions in the aptamer contribute to adaptability in protein recognition and binding. After the binding site on RNA recognizes complementary surfaces on the protein target, one or both might undergo conformational changes, referred to as “induced fit” . Recent research showed that while an aptamer is highly flexible and can adopt a variety of conformations to recognize its target, engagement with the target will select a specific conformation and fix it …”

“…40 In addition, aptamers can be selected toward toxic and poorly immunogenic targets, whereas antibodies produced in vivo cannot be generated to such targets. 40 Indeed, a remarkable aspect of aptamers is that, in principle, they can be generated for selective binding to virtually any target. 8 As shown in Figure 2, the complex tertiary structures of aptamers have extended surface areas for target recognition, allowing for the establishment of tight interactions.…”