UCI looks to counteract virus mutations

April 10, 2020

By Anna Lynn Sptizer and Lori Brandt

While much of the country is worried about flattening the curve through social distancing, bioengineers are preparing to deal not just with the current wave of the coronavirus but future waves and outbreaks.  They want to help researchers and public health officials track and protect against the spread of the virus over time as it mutates.

Biomedical engineer Chang Liu is applying his expertise in genetic engineering and directed evolution to help find potential therapeutic and diagnostic agents for SARS-CoV-2, the virus responsible for the COVID-19 pandemic. Liu’s lab has developed a technique called orthogonal DNA replication, which is capable of continuous hypermutation of genes in an engineered yeast cell. He is using this synthetic genetic system to detect and neutralize a key interaction between the coronavirus’s spike protein and the cellular receptor, ACE2, which acts as coronavirus’ main entry point into the cell.

Chang Liu’s orthogonal DNA replication system is capable of continuous hypermutation of genes. He is using it to develop a protein evolution system that can mimic the immune system and find answers about the coronavirus.

“We are working on an accelerated protein evolution system that can mimic natural immune systems, but that works on a faster pace and is primed for generating high-affinity binding proteins against SARS-CoV-2 and new versions of the virus should they evolve,” said Liu, assistant professor of biomedical engineering. “We will use this system to evolve high-quality nanobodies and ACE2 variants to detect and neutralize the SARS-CoV-2 through binding of its spike protein.”

Such a process could be crucial to fighting current and future waves of the coronavirus pandemic. With this rapid evolution system, researchers will be ready to generate binding proteins against SARS-CoV-2 and future coronaviruses within two weeks of obtaining a target. Quickly evolved high-quality binding proteins can act as critical reagents in detection platforms and as therapeutic candidates for the protection of medical workers before patient-derived antibodies, conventional therapeutics and vaccines are available.

UCI postdoctoral researcher Alon Wellner and graduate student Ming Han Ho are working with Liu on this project, as are biology colleagues Andrew Kruse and Conor McMahon from Harvard Medical School.