Zentek, McMaster announce results for aptamer-based technology

Zentek announcedthat its aptamer platform under global exclusive license from McMaster University has been tested as a potential prophylactic or therapeutic for SARS-CoV-2 in pre-clinical animal models. In repeat trials, the aptamers developed by Dr. Yingfu Li demonstrated similar efficacy against SARS-CoV-2 when benchmarked against a commercial monoclonal antibody. This new aptamer, based on a novel approach, was developed under the exclusive worldwide 20-year license agreement between Dr. Li’s lab at McMaster and Zentek first announced on June 17, 2021. Dr. Yingfu Li’s team developed a series of aptamers with high-binding affinity with the SARS-CoV-2 spike protein. In February 2023, the best performing aptamer against all variants of SARS-CoV-2 was tested in vitro to assess the neutralizing of the virus by the aptamer in Vero cells. With strong results, Zentek was motivated to move into in vivo trials. Dr. Matthew Miller, the Canada Research Chair in Viral Pandemics and the director of the Michael G. DeGroote Institute of Infectious Disease Research designed and supervised all of the pre-clinical trials. The first pre-clinical trial included three groups of mice: Group A, which was a control group and received no prophylactic treatment, Group B, which received a commercial monoclonal antibody that was a leading antibody for the original SARS-CoV-2 strain until it was rendered ineffective due to antigenic changes in Omicron sublineages,and Group C, which received an aptamer designed by Dr. Li’s team. All groups were infected with SARS-CoV-2. After four days, the mice that received the antibody and aptamer treatment had minimal weight loss, while the control group had a 10% body weight decline. In addition, the viral burden of the control group was measured at 10,000 PFU per lung. Significantly, the viral burden was undetectable in the lungs of the mice treated with the antibodies or the aptamer. Based on these results, an additional trial was completed following the same procedure with a lethal challenge dose of SARS-CoV-2 where the mice were once again divided into three groups: control, antibody, and aptamer treatment. The control or untreated group lost 20% of their body weight after four days and all mice reached humane endpoints. The groups receiving either the aptamer or antibody treatment had less than a 5% reduction in bodyweight after the four days. The gross pathological assessment of these lungs at day 4 post-infection indicated that the aptamer, like the antibody, completely protected the lungs from any observable tissue damage. The control group’s lungs on the other hand had evidence of significant hemorrhaging. In addition, the antibody and aptamer prophylactic provided sterilizing protection where no detectible viral titers were measurable, demonstrating similar performance between the commercial monoclonal antibody and the Li Lab aptamer. Aptamers are synthetic single stranded DNA or RNA type molecules that are built from the same building blocks of human DNA or RNA; hence offering a significant positive safety profile and have already demonstrated such safety. The 2018 article entitled “Pharmacokinetics, Pharmacodynamics, and Safety of Aptamers” by Kovacevic et al. stated that aptamers are considered to be generally safe based on multiple studies of aptamers for therapeutic use. Reference to toxicology studies and off-target side effects also lead to the concluding statement that generally, the safety of aptamers is very good. Given the significance of these results and based on the importance of this opportunity, a pre-clinical plan is being formulated for the development of a COVID-19 therapeutic/prophylactic based on the Dr. Li aptamers. Dr. Li is also working on other targets for aptamer treatments, and these are under early investigation.