News and Events

Hypertrans Protein Expression System – What is it, and what are its benefits?

Protein expression systems have been developed for many host platforms with the aim of producing large amounts of protein. These can then be used in a number of applications, such as research, diagnostic and therapeutic medicines.

Eukaryotic expression systems typically contain: a strong promoter to drive transcription (the process of producing mRNA); a terminator, that contains the signals to end the mRNA strand and attach a polyadenylation sequence that aids mRNA stability; and sequences which allow for efficient translation (protein production by ribosomes from mRNA) from the mRNA.

(https://www.youtube.com/watch?v=bTGFsILjZAQ)

The Hypertrans® system is a plant-based expression method developed by George Lomonossoff and Frank Sainsbury at the John Innes Centre and delivers high levels of protein expression in plants. This system was developed through the discovery that mutation, particular sequences in the promoter of the Cowpea mosaic virus (CPMV, a plant virus), resulted in the high-level expression of protein when the gene of interest replaced the native CPMV protein. The CPMV terminator sequences also appear to result in enhanced mRNA stability.

While the Hypertrans® system is based on viral sequences, it does not require viral replication for the transmission or expression. This means that the size of the gene that can be expressed in the system is not limited by the size restrictions of viral systems. In addition, since no viral replication occurs it cannot spread to other plants, meaning there are not the requirements of containment associated with viral replicating systems.

In the Hypertrans® system, the features from CPMV are combined with a gene silencing suppressor. Plants have evolved many ways to control the levels of mRNA present in a cell, thereby making it difficult to generate enough mRNA to produce large amounts of protein. This process is known as post-transcriptional gene silencing, as it effectively silences the expression of the gene. However, nature has provided mechanisms to overcome this suppression, with many plant viruses containing proteins that can prevent this silencing. In the Hypertrans® system, P19 from the tomato bushy stunt virus (David Baulcombe) is co-expressed allowing for enhanced transient expression in plants.

All of the features of the Hypertrans® system have been combined in an easy to use plasmid series (pEAQ), which allow the simple one-step cloning of your gene of interest into a vector which can be introduced into Agrobacterium and expressed in a plant.

 

What are the benefits of the Hypertrans® system and how does it compare to other systems?

The flexible nature of the system enables production to be scaled from small scale research quantities to pilot-scale production very quickly. The speed of the system means that it can rapidly produce large amounts of protein and so it is well suited to rapidly responding to emergencies like pandemics. And…..less time in production equates to significant patent extension, perhaps as much as 12 months.

The technology is disruptive, and to date, there are no licensed products on the market that have been produced in plant systems. To a customer that can be seen as a considerable gamble, but what is true about the system is that a feasibility study to confirm whether the protein of interest will express can be done very quickly and at a fraction of the price compared to more conventional systems. Moreover, accurate likely costs of goods can also be established very quickly because the system is directly scalable, it’s just a case of adding more plants.

There’s also the question around regulatory approval. Conventional systems often face regulatory concerns over product purity and potential adventitious agents from the use of animal-derived raw materials and infection of patients. With plants, these concerns are avoided altogether as no animal-derived products are used in any part of the manufacturing process, either upstream or downstream.

These advantages all culminate in plant expression generally being much more cost-effective and facilitating greater R&D throughput, so surely it’s worth a try?

Leaf Expression Systems Launch First Line of Hypertrans® Research Products

Plant-expression deal for difficult to produce proteins, vaccines, metabolites and natural proteins

29 May 2019: Norwich, UK Leaf Expression Systems, a contract development and manufacturing organisation specialising in the plant-based expression and production of proteins, vaccines, metabolites and complex natural proteins, has announced the launch of its online list of products available for purchase by researchers working within the life sciences and agricultural industries.

The products are produced in Nicotiana benthamiana using Hypertrans®, Leaf’s Agrobacterium-mediated transient expression technology. Hypertrans® is efficient, safe and simple to use to quickly produce proteins, vaccines, antibodies or enzymes in plants.

The products; Bet v 1-A – Betula verrucosa (European white birch) allergen 1-A, Cowpea Mosaic Virus VLPs, Horseradish Peroxidase (HRP) C1A, Human Nucleotide triphosphate diphosphatase NUDT15 (MTH2), MAb Anti-VEGF 165A, Phleum pratense (Common timothy) allergen 1 and Triosephosphate Isomerase (TPI) are all available for purchase for research purposes via its online platform.

Simon Saxby, CEO said ‘We are excited to launch our first proprietary products produced in plants using Hypertrans®. We will continue to add products that are difficult or uneconomical to produce using other expression systems to add to the research tools available to the life science community and which also demonstrate the extreme flexibility and capability of Hypertrans® for the rapid manufacture of a wide range of biologics on commercially viable scales’.

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Contact:

Media

Richard Hayhurst Associates
Richard Hayhurst
Richard@richardhayhurstassociates.com

Leaf Expression Systems
Polly Ferris
Marketing and Communications Officer
Leaf Expression Systems
ferrisp@leafexpressionsystems.com
01603 859298

 

About Leaf Expression Systems

Leaf Expression Systems is a contract development and manufacturing business specialising in plant-based expression and production of proteins, vaccines and complex natural products for research and commercial applications.  It uses Hypertrans®, the proprietary transient expression technology.

The Hypertrans® system allows for the rapid simultaneous production of multiple gene products in a controlled and coordinated manner within the tissues of plants.  Using gene synthesis and modular vectors, new products such as vaccines, antibodies or enzymes can be produced at speed and on a large scale, so it is well suited to be able to rapidly respond to emergencies like pandemics.

Leaf Expression Systems is based in a purpose-built, state-of-the-art facility on Norwich Research Park, that boasts of four environmentally controlled growing rooms, plant potting areas, a plant inoculation area, microbiology/molecular biology labs, protein purification and natural product processing facilities.

 

leafexpressionsystems.com

Plant Bioscience Ltd transfers control of Hypertrans® plant-based biologics and vaccines expression technology to Leaf Expression Systems Ltd

14 May 2019: Norwich Plant Bioscience Ltd (PBL) and Leaf Expression Systems Ltd (Leaf) are delighted to announce a further development in their relationship, with PBL granting Leaf the exclusive rights to sub-license the Hypertrans® transient expression system, the core technology underpinning Leaf’s biologics and vaccines contract development and manufacturing services business. Apart from rights previously granted to PBL’s pre-existing licensees, this effectively transfers to Leaf full control of the Hypertrans® technology and associated patented intellectual property. This extension of Leaf’s rights will ensure that Leaf’s clients are able to use Hypertrans® for the manufacture of their products in multiple geographical locations to meet the needs of individual markets and to enable clients to take advantage of lower manufacturing costs in some of these markets.

Leaf’s CEO Simon Saxby commented “I am delighted that we have strengthened our relationship with PBL and that we can now offer our clients the assurances they need in order to plan for scale up manufacture using Hypertrans® in the locations that are most appropriate for the target indications of their new biologic drugs or vaccines”.
PBL’s Managing Director Dr Jan Chojecki added “Leaf has been outstandingly successful in establishing its technical operations and developing its customer base and partnering activity. Now is the time to put Leaf fully in the driving seat with regard to this important and proprietary intellectual property asset developed originally by Professor George Lomonossoff at the John Innes Centre”.
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For further information, contact:
Polly Ferris, Marketing & Communications Officer.
E: ferrisp@leafexpressionsystems.com
T: 01603 859 298

Notes to editors:

About Leaf Expression Systems

Leaf Expression Systems is a contract development and manufacturing business specialising in plant-based expression and production of proteins, vaccines and complex natural products for research and commercial applications. It uses Hypertrans®, the proprietary transient expression technology, which was originally developed by Professor George Lomonossoff of the John Innes Centre.

The Hypertrans® system allows for the rapid simultaneous production of multiple gene products in a controlled and coordinated manner within the tissues of plants. Using gene synthesis and modular vectors, new products such as vaccines, antibodies or enzymes can be produced at speed and on a large scale, so it is well suited to be able to rapidly respond to emergencies like pandemics.

Leaf Expression Systems is based in a purpose-built, state-of-the-art facility on Norwich Research Park, that boasts of four environmentally controlled growing rooms, plant potting areas, a plant inoculation area, microbiology/molecular biology labs, protein purification and natural product processing facilities.

leafexpressionsystems.com

About PBL
PBL (www.pbltechnology.com) is the intellectual property management and technology commercialization company of the John Innes Centre and others.

For further information please go to:
www.leafexpressionsystems.com and twitter.com/leaf_expression

National Apprenticeship Week 2019

National Apprenticeship Week 2019

To mark National Apprenticeship Week, we asked our talented Apprentice Laboratory Technicians, Joe and Karen, to share their experiences of the programme.

        

Joe Ball

I joined Leaf Expression Systems in August 2017 after finishing my A-levels in Maths, Further Maths and Physics. I chose this route instead of accepting my offer to study a degree in physics because I wanted to gain a recognised qualification and work experience at the same time. I also believe that learning about a topic and then putting that knowledge straight into practice is a great way to learn.

During my time at Leaf I have been taught a lot of theoretical and practical knowledge and techniques like: agroinfiltration, plate streaking, culture growing, protein purification, media/buffer/solution creation, and more. I have also learned a great deal about the safety precautions and training involved and how important safe operating procedures along with risk assessments are in this industry, especially when using expensive and potentially hazardous equipment (if untrained) such as: autoclaves, orbital shakers/incubators, heat stirrers, infiltrators. This is alongside the use of a vast range of chemicals, buffers, solutions and more.

This role has surpassed my expectations and I have learned so much more than I thought I would. It has also developed my skills in areas like team working, communication, planning and research, and self-management to name a few. Overall it has been massively positive experience and I would recommend this route.

 

Karen Annison

I left school with science GCSEs & A-Levels, I wanted to pursue a career in science, but I wasn’t interested in going to university, so I started looking for apprenticeships within the science field.  I spotted the advert for this apprenticeship which seemed like an opportunity to get a qualification through working as I prefer to learn through hands-on experience instead of working in a classroom.

In the 18 months that I’ve been an apprentice, I’ve learned more than I thought I would, and I’ve been able to put practical techniques that I learned at school into use working within this company. The key things that I have learned include writing SOPs and EHS documentation, as well as key transferable skills such as pipetting and microbiological techniques. I also sit on the EHS committee and I am a first aider within the company. I would like to carry on working in the science sector and progress up the career ladder and work through the different fields within                                                          the industry.

 

 

 

CEO Update from Simon Saxby

Since our last update in October 2018, I am delighted to report that a lot has happened at Leaf in just a few short months. We have added some new members to the team to strengthen our depth and capability, we have secured a number of commercial contracts and collaborations with both pharma and biotech companies, and in January this year Richard Hart joined us as Business Development Director to lead the growth of our contract development and manufacturing services business.

As a big supporter of apprenticeship programmes, I am also pleased to report that our two apprentices are about to “graduate” and complete their apprenticeships. Both Joe and Karen have demonstrated the value of combining college-based learning with on the job training, and we are delighted that they are staying with us as valued members of the team.

The global CDMO market is forecast for further significant growth, with some estimates predicting that the global value of outsourcing will grow to over $87.6 billion by 2027. The fact that manufacturing biologics in plants is finally emerging as a genuine commercially viable option for reducing the time to market and the cost of drugs and vaccines to patients means that with our Hypertrans® transient plant expression technology, Leaf is perfectly placed to take a leading role in helping to deliver new and better drugs, free from animal derived products, that will lead to improved patient outcomes in the future.

We are also excited to announce the launch of our Products Page on the Leaf website! The team have produced a number of products that exemplify the production capability of Hypertrans® in terms of yield and functionality, and the products themselves are valuable research reagents which we are making available through our website. Our ‘first wave’ of products include an antibody, and enzyme, a virus-like particle and an allergen – all of which can be found here. We will be expanding the range of products that are available, including products that are difficult to express in mammalian or microbial systems, but which do express well and more cost effectively with Hypertrans® in plants. These will include cytokines, growth factors etc that are absolutely necessary for the manufacture of advanced therapies but are also extremely expensive to produce using current methods.

And last, but certainly not least, we were proud to be selected as a Finalist in the “Excellence in Life Sciences” category in the South Norfolk Business Awards 2019.

These are exciting times for Leaf and we are looking forward to tackling the challenges that we, and everyone else in the industry face, in improving the quality of life of people around the World.

Best,

Simon.