Friday, July 1, 2022

More than covid in RNA tech solutions

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A chapter of this year’s budget outlining a $40 million investment into RNA vaccination research passed with little fanfare. But it was met with much celebration from scientists involved in this area of flexible, rapid vaccination deployment suitable for both humans and production animals. Richard Rennie spoke to Axel Heiser, principal scientist at AgResearch and one of NZ’s few experts in the RNA vaccination field.

As the world waited with bated breath to see how well its rapidly developed covid-19 vaccinations worked, much was made of the ‘new’ messenger-RNA (mRNA) technology that was the foundation for several vaccinations’ success. 

Greater public awareness of the technology, and the $40 million budget injection for an RNA research and development platform, means the technology could be adopted soon to help unlock some lingering animal diseases less likely to be addressed by large offshore commercial drug companies.

Messenger RNA is a technology that has been around for almost 20 years, one which Axel Heiser played a part in helping pioneer, initially with cancer patients.

“The costs of using it were high, about $10,000 a vaccination shot, but this is why the work started off with cancer vaccines, it is where the funding is.” Put most simply, mRNA has researchers taking a virus’s genetic blueprint, or its RNA, and isolating the genes responsible for a particular trait they wish to block or inhibit. 

In the case of covid this required getting the genetic sequence for the protein “spike” the virus used to attach itself to human host cells. 

Isolating that particular “messenger” RNA, it can then be used to give the host cells instructions, such as to build the covid-19 virus’s spikes, but not the virus itself.

Building multiple spikes using the genetic blueprint it has been given means the immune system learns how to attack and destroy the intruding virus when it arrives.

The fact only the protein is produced means the host will not become sick in the process of being vaccinated, while the host cells destroy all spikes and memory cells linger, producing antibodies into the future to offer on-going protection.

As a technology mRNA has proven quick to develop, once the RNA sequence of the virus is known.

Heiser was involved in the first efforts to develop mRNA, in the late 90s with the first clinical trial treating prostate cancer and getting a positive immune response from the vaccination. 

Further work included vaccination trials for brain cancer before he returned to New Zealand in 2010, ultimately joining AgResearch’s infectious diseases team.

“We have always tried to get funding for RNA vaccinations in animals, but it is not an easy path. At present, our first disease we would look at targeting is Bovine Viral Diarrhea (BVD).”  

BVD is a complex, insidious disease estimated to account for about $150 million a year in lowered productivity, sick and dead livestock and thought to be significantly under-diagnosed. 

Vaccines are available, but Heiser says an mRNA vaccine could deliver a prevention with higher efficacy in the field 

The BVD virus has a spike similar to covid’s and scientists feel confident it could be developed given sufficient funds within a couple of years.

“People often say how quickly the likes of the Pfizer virus came out in response to covid, but really this reflected the significant amount of funds committed in a short time. With enough money you can move this technology along quickly.”

Part of the challenge for a small pastoral country like NZ is the likelihood large multi-national drug companies will not develop vaccine solutions themselves, given the relatively low volume and low margins pastoral production animal vaccines offer against their high development costs.

Heiser says it is possible such companies will wait until the heavy lifting research behind mRNA vaccination technology is developed, before taking it on commercially.

But he is also hopeful the new $40 million fund may see NZ commercialise its own vaccination products, given the new fund has a specific goal to bridge engagement between researchers and industry partners to test and commercialise new approaches. 

“The beauty of mRNA is you do not need large 100,000 litre fermenters to make these vaccines.”

The relative ease of identifying, packaging, and inserting mRNA vaccination tech opens the door to multiple disease control options, including Mycoplasma bovis, Johne’s disease, foot and mouth and ovine pneumonia, a huge health constraint on sheep production.

Methanogen vaccinations may also benefit from mRNA if their more complex means of working across the rumen, bloodstream and saliva can be overcome.

Researchers are also hoping the recent funding boost will help support “micro-RNA” research, technology that may prove the diagnostic disease tool of the future. 

They can also work as therapeutics, helping drive the optimal deliver of treatment for disease specific release, with minimal toxicity.

“We are also confident there is work involving the human side of vaccinations, while our BVD project will also be planned around the next 18 months.”

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