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Decoding RNA’s mysteries

Novel COVID-19 vaccines and some diagnostic tests use messenger ribonucleic acid (mRNA). Aaron Engelhart investigates ways to track the nucleic acid.

Ribonucleic acid (RNA) has received a lot of press recently. Not a huge surprise as RNA plays a critical role in cell function, decoding genetic information and creating proteins. But it’s in the news because of the role it plays in COVID-19 vaccines. The first COVID-19 vaccines approved for use developed by Moderna and Pfizer-BioNTech rely on messenger RNA (mRNA). This is a different approach compared to traditional vaccines, like the one for seasonal flu.

Despite significant progress over the last two decades, scientists continue to work to better understand RNA. Genetics, Cell Biology, and Development Assistant Professor Aaron Engelhart’s lab studies foundational biology and how it relates to human diseases. They work to understand how to replicate, track and package RNA. Their research is fundamentally linked to combating the COVID-19 pandemic, despite not identifying as immunologists or virologists. We recently caught up with him for a Q&A.

What is different about an mRNA vaccine?

Traditional vaccines, like one used for the seasonal flu, use inactivated or weakened form of the targeted virus to prime the immune response. mRNA vaccines use a very different approach. These vaccines contain instructions for cells to create a protein or part of a protein that looks like the virus, ultimately eliciting an immune response. For COVID-19, it’s easily recognizable because of a “spike protein” on the virus’s surface. So the mRNA vaccines contain instructions for that protein which train the immune system to respond if and when it is exposed to COVID-19. 

Why is tracking RNA so important? 

For over three decades, scientists have used a fluorescent protein to tag proteins. Fluorescent proteins are ubiquitous tools in modern biochemistry. This makes it much easier to see how they move, change and interact with other proteins in cells. RNA is trickier to tag and track. This means it’s much harder for scientists to study it and it remains a bit of black box. Our lab is working to develop a genetically-encoded fluorescent sensor to detect chemical communication between cells.

How does tracking RNA relate to diagnostics? 

Before the pandemic started, we were working on using fluorescent tags to track RNA, an approach to test for viruses. In late March 2020, we added a COVID-19 lens to that work. We developed a tool that uses this idea and it does have an advantage missing in more traditional COVID-19 tests. Those tests utilize a technique that amplifies DNA — and comes with an expensive machine. After someone is swabbed, the samples are sent to a processing site which can mean long delays for rural areas. The test we developed is more affordable and quicker than traditional COVID tests.

What’s another challenge you tackle in the lab?

When thinking about translating lab discoveries into therapeutics, delivery is a key piece of the puzzle. If you want to put nucleic acid (like DNA or RNA) into a cell, you have to package it. You can’t just insert the nucleic acid freely into a patient. For the Moderna and Pfizer-BioNTech COVID-19 vaccines, they leveraged lipid packaging, which basically amounts to a fatty compartment. In the lab, we experiment with lipids that look a lot like cell membranes, and create cell-like compartments. Down the line, these findings help inform future vaccine development.

— Claire Wilson


March, 2021