How to Fight COVID-19... with a Virus

  Researchers have been working on vaccine candidates for COVID-19 for months now. Some of their work looks like traditional vaccine develop...


 Researchers have been working on vaccine candidates for COVID-19 for months now. Some of their work looks like traditional vaccine development, albeit on a super sped-up timeline. But other research groups are trying some more creative approaches to therapy... including ones that involve directly editing our genes.


 This is known as gene therapy, and it’snot as outlandish as you might be thinking. The outlandish part is that viruses are one of our primary tools for gene therapy -- meaning we might be able to solve our current virus problem… with a virus. However, this approach comes with some uncertainty and a significant price tag, so it’s hardly a sure thing. Here’s how it might work. The goal of a vaccine is to safely expose your immune system to antigens derived from an infectious agent like a virus.


 After vaccination, our bodies recognize this antigen and know how to defend against it for a period of time. That might mean exposing our bodies to a weakened or inactivated form of a virus or bacterium that our immune systems can produce antibodies against it. But there are plenty of other ways we can end up with immunity. For example, some doctors are already using convalescent plasma from recovered patients to transfer their antibodies to patients who are critically ill. But that’s still in the testing stages.


 Some of the vaccine candidates making swift progress in clinical trials are based on the nucleic acids DNA and RNA. The idea is to teach our cells to make viral antigens and to show them to our immune system -- rather than bundling the antigens themselves in a shot. One hurdle to this idea is getting that genetic code into cells. RNA, in particular, can get broken down pretty quickly in our bodies.

 But the concept is solid: teach cells to make a specific part of the virus-like the spike protein, which SARS-CoV-2 uses to invade our cells. So rather than injecting patients with just the code, another approach is more akin to fighting fire with fire. Or a virus with a virus. After all, viruses are really efficient injecting genetic material into host cells. It’s what they do -- they’re really just little nucleic acid delivery packets, with instructions for making more packets. And we can reprogram those instructions.


 So they’re actually perfect if we want to introduce genetic instructions into a cell. But we need a virus that won’t also make us sick, which is why adeno-associated viruses, or AAVs, are the DNA vehicle of choice. AAVs are little viruses that don’t cause disease, further genetically engineered to deliver their payload without making more of themselves. They’ve already been used in the past in efforts against other corona viruses.


 Different AAVs tend to infiltrate different tissues, and since COVID-19 affects the lungs, we'd need to find an AAV that can get to our airway. Some of the AAVs scientists have tested were able to get into human respiratory cells in culture, but they haven’t been tested in actual humans yet. And since an AAV is just a tiny DNA delivery unit, we could swap out different sequences and test them all very quickly.

 AAV-based gene therapy for other diseases has already been approved by the US Food and Drug Administration, which could speed the implementation of a version of this therapy for COVID, at least according to some. The potential downside is that this style of gene therapy permanently edits cells. Not as permanently as you might be thinking. It wouldn’t target our germ cells, meaning we wouldn’t pass this DNA down to our kids.


 We don’t yet know all of the cell types we would need to target, but the changes probably wouldn’t stay with us for a lifetime. This means any kind of AAV-based therapy we develop for SARS-CoV-2 would only be a temporary fix. But it might offer us some level of protection while we’re waiting on a more permanent vaccine.


 But we can’t rule out other long-term side effects from directly tinkering with our DNA, even if it seems like it should be safe based on what we know. On top of all that, there’s the cost. Since the currently approved AAV-based drugs treat extremely rare genetic diseases, they come with an inflated price tag. But since an AAV for COVID-19 would be a much larger market, the cost would hopefully be lower.


 Now, will gene therapy for the novel coronavirusever actually be a thing? We have some good news on that front. Researchers in Massachusetts recently announced plans for a COVID vaccine clinical trial using AAVs. They’re in the preclinical trials right now, and if all goes well, they’ll move into human trials later this year. This means if we do ever see AAV therapy, it will still be a while. But it’s definitely one of the more creative efforts out there -- and we need to try everything we’ve got. 
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