Liver as a bioreactor for robust production of SARS-CoV-2 neutralizing antibodies

Cullis, Pieter R | $237,445

British Columbia University of British Columbia 2020 CIHR Operating Grant

Passive immunization is when the serum of recovered patients is transferred to patients suffering from the disease. This serum contains the necessary antibodies produced by the recovered patient’s immune system to fight-off the infection. However, this approach to treating infections requires large amounts of convalescent serum, which is difficult to obtain. A novel and promising strategy would be to artificially produce the selected antibodies that would fight-off the infection. However, antibody manufacturing at large scales is a fundamentally slow and laborious process lacking the infrastructure within Canada. Here, we use a more scalable, well understood, already established and approved platform technology, namely lipid nanoparticles, to deliver messenger RNA to the liver, where this antibody will be produced through the natural biochemical processes of the human body and secreted into the systemic circulation. The liver naturally produces over 90% of proteins in blood circulation and has the remarkable ability to produce antibodies also. We will modify the mRNA sequence that encodes the antibody so that it can access the lumen of the lungs where it is most needed to protect epithelial cells from being infected by the virus. The end result is a formulation that generates the antibody in the liver and will afford robust immune protection against virus in the blood and in the lungs. Our proposal requires funding to support the generation of the mRNA material, preparation of the nanoparticles using well-established and scalable procedures, and subsequently testing them in mice. This technology expands upon existing lipid nanoparticle technology that is currently being evaluate as a COVID‑19 vaccine in phase II clinical trials (Moderna, CureVac, BioNTech).

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