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The 2020 COVID-19 pandemic has triggered tons of activity in biotechnology, almost causing a mini-Renaissance in novel methods to improve the human condition, vaccines, etc. Among this activty, there has been a resurgance of interest in Dr. Todd Rider’s DRACO, acronym for double-stranded RNA activated caspase oligomerizer. There have been a Change.org petition1, and even Reason (the longevity researcher) mentioned DRACO in his relatively recent “How to Start a Biotech Company in the Longevity Industry” guide published on Fight Aging!2. Shortly thereafter, a startup company (Kimer Med) was founded inspired by DRACO3.
This post will discuss existing DRACO data and its promises and challenges when applied to the current COVID-19 pandemic. Much of the content from this post comes from research I’ve done and discussions with industry colleagues.
DRACO (double-stranded RNA activated caspase oligomerizer) is a novel broad-spectrum antiviral drug. As a high level overview, the technology is based on the premise that most infected cells can be differentiated based on the length and type of RNA transcription helices. Why does this work? Becauses viruses are parasitic in that they rely on infected human cells to replicate their own sequences.
There are few viruses including Hantavirus (which will kill you in hours anyway) that won’t be affected by DRACO. Once target cells are discovered, apopotosis-signaling molecules are bound to the cell to signal for cell death.
To date, this method has only been tested benchside in cell cultures and in vivo animal trials still have to be performed. I believe there may have been experiments, but haven’t yet seen/studied the results (blog may be updated).
Many challenges are outlined quite well by Karnofsky & Somerville in Open Philanthropy6 and I encourage the readers to read that as well.
One of the most obvious but overlooked challenges specific to this method and how it relates to the SARS-CoV-2 coronavirus is DRACO’s mechanism of killing all cells that are candidates for being infected.
Assuming the technology works in vivo (there are yet to be any studies in model organisms), we are still extremely concerned about the potentially severe lunge damage caused by coronavirus. Lung tissue is difficult to regenerate and DRACO’s primary mechanism of action (apoptosis) will only further exacerbate permanent damage to lung tissue.
There are additional concerns that mass disorderly destruction of cells and having their insides splatter everywhere may cause a cytokine storm, possibly triggering an overproduction of neutrophils.
The Principal Investigator, Dr. Todd Rider, mentions in a publication in PLoS One and an oral presentation at the SENS Research Foundation that DRACO is able to cross the blood-brain barrier7, though we’re unsure about other parts of the body with minimal bloodflow (like joints), but perhaps that isn’t as relevant.
Finally, this is not a vaccine but a therapeutic (semantics are important). Vaccines are a precautionary or preventative measure that utilizes a piece of the virus or inactive virus to simulate the body’s response to fighting the virus (building active immunity). This won’t help someone who presently is infected with the virus. For that, you need a therapeutic or treatment to help fight off the infection. DRACO does not appear to be similar to an antibody therapy, which helps the body fight back. This could mean that the immune system won’t have “memory” to combat the virus and each infection may have to be treated de novo.
I think the approach is ingenius, though a bit crude in that it basically carpet bombs everything that meets a particular set of criteria.
In our opinion, the solution with the highest probability of success, speed to market, and optimal impact will be an antibody therapeutic, and this is what we’re seeing in existing COVID trials from large pharma companies. Unfortunately the typical issues remain around administering the antibody therapy. For example, the Moderna therapeutic required extremely cold temperatures, making it challenging to administer the drug without potentially harming blood vessels.
Critics have mentioned that, given its potential risks, DRACO likely will not gain traction unless humans are faced with severely deadly viral infections6 like Ebola. We remain open minded.
Inspired by other researchers, we are much more excited about nonhuman applications of DRACO such as for livestock, which we believe will be the killer application8.
Guo, C., Chen, L., Mo, D. et al. (2015) DRACO inhibits porcine reproductive and respiratory syndrome virus replication in vitro. Archives in Virology 160, 1239–1247. https://doi.org/10.1007/s00705-015-2392-4 ↩