Aptamers can be thought of as analogs of antibodies entirely composed of nucleic acids (DNA or RNA). They can be used in a wide range of applications but they have limitations due to their inherent chemical nature. The Laboratory for Bioorganic Chemistry of Nucleic Acids demonstrated that chemically modified aptamers could distinguish P. vivax from P. falciparum, both parasites responsible for malaria. These results open the development of novel clinical diagnostic tools.
Aptamers can be thought of as analogs of antibodies that are entirely composed of nucleic acids (DNA or RNA). These structures can form specific complexes with protein targets that offer a wide range of potential applications. But aptamers have several limitations as a result of their natural composition. Introducing chemical modifications is a way of overcoming some of these problems. In a recent article, The Laboratory for Bioorganic Chemistry of Nucleic Acids has used, together with researchers at the University of Hong Kong, chemical modifications called cubane that are entirely absent from living systems but widespread in medicinal chemistry to improve the properties of aptamers. Particularly, they demonstrated that the modified aptamer can be useful in distinguishing P. vivax from P. falciparum, both parasites responsible of malaria, in diagnostic assays mimicking a clinical situation. Identifying the Plasmodium species, especially P. falciparum (the most virulent) and P. vivax (responsible for subacute, chronic malaria) remains difficult and thus our discovery bodes well for the development of novel diagnostic tools. Importantly, together with the Crystallography Platform of the Department the researchers have resolved the crystal structure of the aptamer-protein complex and demonstrated that introducing cubane moieties into DNA enabled the aptamer to interact with proteins in new ways.
This study is part of the Vaccinology and Immunotherapy Initiative of the Institut Pasteur's strategic plan for 2019-2023.