Increase potency, decrease COGS
Self-amplification isn’t discussed as broadly as it should be given the vastness of literature and milieu of current clinical trials to date.
Healthy humans are a wonder. Their bodies sense danger (viruses, cancer, bacteria), kill danger, develop from fetus to adult, repair wounds, and so much more. Healthy bodies should be the standard for what drugs of the future look like. Drugs should sense, respond, heal, regrow, and do this more and more cheaply over time. Human bodies are diagnostic and therapeutic and our drugs eventually should be too - e.g. cell therapies, tissues therapies, organ replacement.
In the journey to this future there are improvements that can be made to our current modalities to make them look closer to living systems. A core step closer to living, breathing drugs is self-replication. Eg. how you make the drug produce more of itself in humans?
In this vein, many papers have come out in the past years specifically on self-replicating mRNA therapies (saRNA). Whereas mRNA vaccines only encode one COVID spike protein, saRNA vaccines encode for RNA replication machinery + a COVID spike protein, enabling the RNA to replicate itself in your cells. What this means is that a materially small amount of saRNA (5 μg) can have the same effect as mRNA at 30-100 μg.
Incredibly, there’s already an approved COVID saRNA vaccine in Japan and Europe that uses this technology, called Kostaive. The company that developed it is a small cap biotech, Arcturus ($ARCT) but has had limited uptake ($28M revenues for Kostaive in 2024, company decreased revenues significantly in 2025). Kostaive also has similar level of side effects.
There’s other preclinical work on saRNA on heart attack repair, Zika, Ebola, HIV, and Toxoplasma gondii. Tissue repair seems to be a good, acute use-cases from wounds, to spinal cord injury to bone regeneration there acute factors that could be secreted to continuously dose during this period.
saRNA in vivo cell therapy could add durability to the response of CAR-T or saRNA could allow for better delivery of gene therapy.
Other Thoughts
