Nature Tech brings DNA vaccines a step closer
prospect in drug development for many years, held back by problems
with effectivness and difficulties in production. But this could be
about to change, reports Phil Taylor.
US company Nature Technology is due to announce positive results from two projects aimed at increasing the effectiveness and productivity of DNA vaccines this week at the American Society of Gene Therapy conference in St Louis, Missouri.
"DNA vaccines represent a bold new way to immunise humans against infectious diseases," said company president Clague Hodgson, "But their effectiveness up to the present has been borderline, and the science requires quantum forward leaps in both efficacy and production in order to reach practicality."
An advantage of DNA vaccines is the ability to safely expose humans to antigenic DNA molecules in the absence of traditional (weakened or killed) pathogens, such as viruses or bacteria. However, in addition to effectiveness, the vaccine must be produced in great quantities and at a reasonable cost of no more than a few dollars per injection.
Nature Technology scientists Jim Williams and Aaron Carnes have made strides forward in tackling the efficacy and productivity issues. Williams' team have used a combinatorial technique known as Gene Self-Assembly (GENSA) to optimise many components of the DNA vaccine backbone, reducing its size by 40 per cent, increasing both the potency and the vaccine's ability to express antigens at comparatively higher levels in both cell culture and animal models.
By expressing the antigen genes via a number of different pathways in so-called mixed-mode presentation using the firm's DNAVaccUltra vaccine system, it is possible to boost exposure of the host's immune system to the foreign proteins, according to Williams.
Meanwhile, the team led by Carnes have produced gains in productivity by increasing the actual yields of the DNA plasmids that can be obtained from bacterial fermentation, the process used to manufacture DNA in large quantities.
"Just a few years ago, we were happy to obtain a hundred milligrams per litre," Carnes said. "Now, it is possible to obtain improved yields of over a gram per litre, and we continue to see gains as we learn more about the upstream fermentation process."
Ongoing work is aimed at streamlining the vaccine production process through genetic engineering of the bacteria that make the DNA. This approach is designed to turn the bacteria into programmable factories, both for growing, and for processing, large quantities of vaccine DNA, according to Williams.
