Some time ago, the folks at openphilanthropy.org posted a long article with their objections against DRACO: https://www.openphilanthropy.org/informal-writeup-dracos-potential-antiviral-treatment
No one has yet undertaken a rebuttal, so I thought the time is right. I can't say I'm thrilled about the idea of posting and discussing a link with so much misinformation in it, but given the likelihood of it coming up in any serious Google search or due diligence investigation, it's better to just address it head-on. I'd like to discuss each objection in a detail when I can, so this will be a thread, not just one giant post.
Chris Somerville spent 2 hours reading about DRACOs and then discussed for about an hour with Holden.
Chris, who is not a virologist, emailed a friend with knowledge of virology about DRACOs for a quick opinion.
In other words, the authors aren't experts, and only spent a few hours thinking about things. This gets more obvious as time goes on.
Complicated delivery: For DRACOs to work as a therapy, there needs to be an efficient method for therapeutically delivering proteins inside of cells in intact animals. Protein motifs (PTDs) that can induce uptake by cultured cells were used in the Rider paper and have been widely used experimentally. By contrast, delivery of therapeutic proteins into cells in live animals is relatively poorly described in the literature.
Protein transduction tags (PTDs) were demonstrated in Rider's paper as working effectively in live mice. The paper describes successful and safe treatment of mice against Influenza H1N1 using DRACO, including tags to deliver the protein into cells.
In addition, earlier research showed the effectiveness of transduction tags in live mice. For example:
The graphic above shows how a transduction tag delivered a protein into a wide range of tissue types in mice, including the brain (so it passes the blood-brain barrier), and that there were no side effects in these mice after 2 weeks of use.
On the left in the graphic above, a fluorescence study visually shows the effectiveness of transduction tags at carrying DRACO into human lung fibroblast cells. With the TAT tag, as above, the concentration of the protein in the nucleus appears higher than the cytoplasm, although there is still a significant amount in the cytoplasm.
The diagram also shows how the concentration of DRACO in cells increases over time, first appearing at about the 10 minute mark, reaching a maximum after about 1.5 hours, and lasting for at least 11 days.
The ultimate test of the effectiveness of transduction tags was the fact that DRACO performed as expected against 15 different types of viruses in 11 different tissue types, and against 3 different viruses in mice (only Influenza was mentioned in the paper; the other two came later). As in the prior studies, the DRACO-treated mice were happy and healthy:
Is it possible that there are some cells or tissues which transduction tags won't reach in adequate quantities when our compound is injected, ingested or inhaled? Sure, it's possible, although you could say the same thing about any drug and administration method. But to say the mechanism is "complex" and "poorly described" in animals is disingenuous at best. It's actually a simple, safe and extremely elegant cellular delivery mechanism.