Not long ago, the synthetic DNA seemed to have a brilliant future as potential replacement of the plasmid DNA used for gene therapies. The increasing number of gen therapy projects in-progress, boosted by the success of different treatments for its commercial distribution, depicted a promising landscape for smart technologies that, involving much lower volumes and apparently less operational complexity than plasmid production, clearly identified a business opportunity.

From 2019, a few initiatives were added to the existing ones, offering a product that was available for customer quite straight forward, avoiding the queue necessary to obtain good plasmid from a relevant supplier. Not only, due to its simplicity, the synthetic DNA promised to be safer, free of undesired sequences and better characterized than plasmids. Some of these new companies has put the synthetic DNA in clinical trials.

However, five years later, all the energy exhibited by synthetic DNA companies seems to have evaporated, with some exception. What has happened? Why this lost of interest or this lost of target hitting by those developers/manufacturers of this new technology?
It is true that the market environment has not been the most favorable for a sector which is very much dependant on finance rounds, the Russia-Ukranie war and the endless problems in international commerce did not help, but the product is still good. Analytical results are not an opinion and they clearly show that synthetic DNA is free -or almost- of bacterial sequences. The practice demonstrates that huge mounts of synthetic DNA can be obtained in a surprisingly short periods of time, where is then the problem?

In my opinion there are a few points that may explain this decay of the synthetic DNA:

1. There are products in the market produced with plasmid, which means that plasmid is good enough for regulators. Against such a business card, you need to do an extraordinary effort to defend a new product and make it attractive enough to make therapy developers assume the risk involved in the novelty.

2. When the product is new, the manufacturer needs to assess the customers on the use of this product closely and patiently, invest time and resources and go side by side with the therapy developer to facilitate the risk mitigation.

3. There is a regulatory front that cannot be ignored, where the simplicity of the synthetic DNA should have a clear advantage versus the plasmid. Have the manufacturers of synthetic DNA profited of this potential?

Finally, there is a niche in my opinion waiting for the synthetic DNA, although is not clear how long it may last. I am talking about the association of synthetic DNA with non-viral vectors, another emerging technology. Both together could make a brilliant solution of the synthetic biology applied to gene therapies, but compromised investors, strong determination and clarity of ideas will be necessary. Do they exist?

 

Alfredo Martínez Mogarra

Chief Scientific Officer

Biotech Academy in Rome