HotHouse Therapeutics harnesses plants to develop next-gen drugs

People are familiar with the healing and medical benefits of many plants such as chamomile and aloe vera but, according to the researchers, this is just the tip of the iceberg. There is great potential for new discoveries as we learn more about how plants produce different kinds of chemicals.

Plants are excellent chemists, so there should be huge opportunities to discover the natural products they create. Until recently, the vast majority of the compounds that plants produce have not been accessible and chemical synthesis of useful molecules from plants has often been difficult, or indeed impossible.

However, researchers from the John Innes Centre at Norwich Research Park think that they have unlocked the code. Led by Professor Anne Osbourn OBE, recognised as a world-leading expert in this field, the researchers are using engineering biology to exploit high potential that plants have for creating new natural treatments.

Following this breakthrough, Anne and her team set up HotHouse Therapeutics, with the aim of translating her lab’s research into a commercially sustainable business that will use specific plant genes to create synthetic ‘recipes’ for new molecules. Pharmaceutical companies can then develop these into new drugs and treatments.

The company is currently finalising a substantial investment and will be based in Norwich, where it will employ six researchers at the outset, including two early career researchers from Anne’s lab.

This innovative work is very well aligned to the UK Government’s priorities that encompass engineering biology. That’s because the end products will benefit society in a range of ways. Locally, this growing sector will create jobs and inward investment to Norwich. It will also contribute to the world-leading profile the city already has in plant science.

Anne’s research is focussed on understanding how plants interact with their environment. She is working to discover why and how plants make molecules to protect themselves against pathogens.

Many of these chemicals have interesting biological impacts and can potentially be made available for human use as new drugs or other useful compounds. However, they are often highly complex and cannot be made in a laboratory by chemistry alone.

The solution is biosynthesis; using a plant’s own genetic machinery to make drugs in a lab. There is a three stage process to this.

Firstly, the pathway genes needed for biosynthesis of the targeted molecule need to be identified. Secondly, these genes need to be introduced into a suitable host – a ‘biofactory’. Finally, the resulting chemical needs to be made.

Finding the genes for plant natural pathways is challenging, but rapid identification of pathway genes in plant genomes is now possible thanks to two recent developments.

The number of genome sequencing facilities for plant species, such as the Earlham Institute at Norwich Research Park, has grown rapidly across the globe. Plant genome sequences harbour the information needed to work out how plants make chemicals.

In addition, significant advances in computational methods now enable scientists to predict which of the thousands of genes within plant genomes are important for making chemicals.

This means it is now possible to create a ‘toolkit for making molecules’ and thus for making drugs by biosynthesis.

This has already been successfully demonstrated. Anne’s lab has been working to decipher how immune-boosting compounds are produced by the Chilean soapbark tree. These compounds are used in vaccines to stimulate an immune response in humans to conditions like shingles, Covid-19 and malaria.

Because of the increasing demand for these types of molecules, known as adjuvants, there has been increasing interest in finding ways to source the compound that do not depend on extraction from the bark of the tree, which grows in the wild in Chile.

To address this challenge, Anne’s lab has sequenced the genome of the tree, identified the genes needed to make an advanced molecule QS7, and have shown that it is possible to put these genes to make ‘free-from-tree’ vaccine adjuvants (used to increase the efficacy of certain drugs). This opens the way to make next-generation vaccine adjuvants that are tailored for optimal immunostimulatory activity without relying on the tree as a means of production.

Now that scientists can successfully sequence plant genomes and use computational analysis to identify key genes that can be included in synthetic compound production for drug manufacture, the commercial value and recognition of this has increased.

Anne said: “One of the greatest challenges to the human race is to develop new drugs quickly enough to counteract the many diseases and conditions that can impair or even end lives. Being able to tap into the plant world’s ingenious approach to creating molecules that can offer the valuable ingredients needed for the new drugs will be invaluable.

“The ability to produce high-value molecules synthetically in a large-scale lab facility will enable environmentally sustainable production of drugs for which supply is limited and of new-to-nature drug leads within a rapid timeframe, which make it very attractive for the pharmaceutical industry.

“Our intellectual property (IP), that we will be able to sell under licence to partner companies, is our knowhow and systems to identify and optimise the specific molecules needed to manufacture a new drug. We will work with partner companies to take our drug leads forwards and put them through clinical trials. We hope to grow rapidly here at Norwich Research Park over the next five years to a position where we are employing up to 50 people.”

Roz Bird, CEO of Anglia Innovation Partnership LLP, the science park management organisation of Norwich Research Park, said: “HotHouse Therapeutics is a brilliant example of how world-leading research being carried out here is starting to realise its commercial value where there is a real global human need for it. Anne’s work is rightly recognised around the world as being groundbreaking and this could be a real gamechanger for how we deal with diseases and medical conditions.

“We are really looking forward to supporting Anne and her team in making HotHouse Therapeutics a real success, further demonstrating the potential Norwich Research Park has for being a great place to start and grow a business.”