Broadly neutralizing aptamers to SARS-CoV-2: A diverse panel of modified DNA antiviral agents

Amy D Gelinas; Tiong Kit Tan; Sai Liu; Javier G Jaramillo; James Chadwick; Adam C Harding; Chi Zhang; Brian E Ream; Chelsea N Chase; Matthew R Otis; Thomas Lee; Daniel J Schneider; William S James; Nebojsa Janjic

doi:10.1016/j.omtn.2023.01.008

Broadly neutralizing aptamers to SARS-CoV-2: A diverse panel of modified DNA antiviral agents

Mol Ther Nucleic Acids. 2023 Mar 14:31:370-382. doi: 10.1016/j.omtn.2023.01.008. Epub 2023 Jan 21.

Authors

Affiliations

¹ SomaLogic, Inc., 2945 Wilderness Place, Boulder, CO 80301, USA.
² MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK.
³ James & Lillian Martin Centre, Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK.
⁴ Department of Biochemistry, University of Colorado, Boulder, JSCBB, C1B90, 3415 Colorado Avenue, Boulder, CO 80303, USA.

Abstract

Since its discovery, COVID-19 has rapidly spread across the globe and has had a massive toll on human health, with infection mortality rates as high as 10%, and a crippling impact on the world economy. Despite numerous advances, there remains an urgent need for accurate and rapid point-of-care diagnostic tests and better therapeutic treatment options. To contribute chemically distinct, non-protein-based affinity reagents, we report here the identification of modified DNA-based aptamers that selectively bind to the S1, S2, or receptor-binding domain of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein. Several aptamers inhibit the binding of the spike protein to its cell-surface receptor angiotensin-converting enzyme 2 (ACE2) and neutralize authentic SARS-CoV-2 virus in vitro, including all variants of concern. With a high degree of nuclease resistance imparted by the base modifications, these reagents represent a new class of molecules with potential for further development as diagnostics or therapeutics.

Keywords: COVID-19; MT: Oligonucleotides; SARS-CoV-2; SELEX; Therapies and Applications; aptamer; modified DNA; variants of concern; viral neutralization.