2021 is set to be an interesting year for gene editing. Gene therapy research is in its adolescence, and the ups and downs are played out almost every day, with plenty of innovative breakthroughs and a few regulatory setbacks. With lots of unknowns and much to be excited about, we spoke with Jon Moore, Executive Chair, Pencil Biosciences to find out more.
Pencil Biosciences is developing a next generation gene editing technology. Can you tell us a little bit more about what you are working on?
There are many, many different types of gene editing technology, each of which is useful for different applications. CRISPR, Cas-9, TALENs, Zinc Fingers, they all have a part to play in experimental biology, therapeutic development and so on.
At Pencil, we’re developing a new gene editing/gene modulation technology with the aim of overcoming some of the issues currently facing CRISPR Cas-9. Our approach will be compact, enabling packaging into delivery vectors, highly specific and have low immunogenicity, making it easy to deliver and ideal for editing cells in the human body.
In such a crowded space, how does your technology stand out from the rest?
Like all gene editing technologies, you could use our innovation in a wide range of applications – research, agriculture, industry, medicine – there is a lot of demand for what we are offering.
Users of any gene editing technology for therapeutic research are looking for something that works, will get the job done, is not extortionately expensive and will not be unnecessarily held up in regulatory issues. Once you have found a technology that meets these criteria, you then need to get approval to use it in vivo for medical applications.
This is where size, immunogenicity and specificity are important, as your application is going to be operating in-body. This is the niche our technology will fill.
You mentioned in-body gene editing. Can you tell us a bit more about this area of work?
Most gene editing for medical applications is currently taking place outside the human body, with the product subsequently administered to the patient. We think our technology has an edge for in vivo gene editing.
For some applications, suppressing or repairing genes within the body’s cells is the best route to a sustained therapeutic effect. Some emerging therapies are using RNA interference delivered with AAV to knock down specific proteins to treat or manage conditions like Huntington’s. With non-dividing cells such as neurons this is fine. However, if you wanted to use this approach to target cells that can rapidly regenerate, such as liver cells, the genetic agent would be diluted out and treatment would need to occur again. To target dividing cells permanently, you need to make a permanent change. CRISPR and related technologies can do this, but this application is in its very early stages.
Currently, most CRISPR editing is conducted on blood cells to treat conditions like sickle cell anaemia or to edit T-cells to fights cancer. In terms of repairing an organ or fighting neurodegeneration we are still at very early stages. We hope our technology may be able to change this.
How significant do you feel the impact of gene editing will be on human health care and over what time frame do you think we are working to?
There are some very powerful gene editing technologies already in use and these will undoubtedly have an impact on the way we treat disease. However, the time frame for this change really depends on the therapy or disease area you are looking at.
For example, there is a lot of promising work around using gene editing to treat blood diseases. This has been an area of early interest because you can take the blood out of the body, edit the relevant genes, then cycle it back into the body, thereby avoiding many of the challenges inherent in in vivo editing. Most of the gene editing companies are working on sickle cell disease and thalassemia and CRISPR Therapeutics has reported excellent initial results for their CTX001 therapy, where symptoms have been alleviated in treated patients for more than a year. This may be an area where gene editing could soon make a tangible difference to health care.
The sticking point with gene therapies is always going to be the cost. When you look at the cost implications for widespread cell therapies for cancer, where hundreds of thousands of dollars are spent on just one treatment, it is daunting. This is where, as ever, more research and time will be needed.
As a company licensing the use of its technology, robust patents are essential. What advice could you offer regarding IP in Biotech?
The biggest thing is having access to the appropriate experts; there is an art to licencing a technology in this space which is its own specific skill. You can think of it slightly like playing a game of chess – you need the right strategy to make sure that your innovation is protected.
For your innovation to be patented it needs to be useful, novel, and inventive, but crucially, all these things need to be demonstrated. For us, we are primarily trying to protect what we currently have by clearly demonstrating what sets it apart from what has gone before. However, to give us scope to expand in the future, we also want to try to expand the reach of our patent as much as possible to allow us room to grow. This expansion requires new data or a very good argument.
All this has a substantial input on the focus we put on different aspects of our company and the experiments we run.
Water-tight patents must be a priority. Especially for a young company, you need to do things in the right order, and you need to take your time. There is a balancing act here: you need to make sure you are legally protected before you race ahead with the science, but you need the science to make your case for a patent. This brings us back to the need for expertise and guidance through the process; you need to choose the right people, both within your team and in your patent attorney.
What do the next few years look like for Pencil?
Currently, we are focused on the technical and scientific, trying to pull off something that is a very difficult technical challenge; it is a lovely puzzle that is a privilege to try to solve. Optimising the technology is the main challenge. Once we have completed this phase, we will look at which lineages of cells or which flavour of gene editing it is most suited for. Then we will be looking for disease experts and motivated patient advocates to join our ranks.
Once we have gained this momentum, we aim to secure partnerships to provide funding, but more importantly to share knowledge, expertise, and inspiration.
We are highly fortunate in having an incredibly diverse and motivated team with a wide range of skills and backgrounds. These talented scientists have been brought together by the mission and vision of Pencil, inspired by the potential impact of the technology to join us on the journey.
We are conducting inventive engineering rather than repurposing a natural system that could offer incredibly exciting breakthrough innovation. All I can say is watch this space!
About Pencil Biosciences
Pencil Biosciences is a seed-stage company based at Alderley Park in Cheshire that aims to develop a flexible, highly-specific and highly deliverable gene editing technology.
About Jon Moore
Jon Moore is a biochemist and cell biologist by training who has previously served as Head of Biology at the structure-based drug discovery outfit Vernalis and as CSO of gene editing tools and services company, Horizon Discovery. He is currently an Operating Partner at Advent Life Science and also CEO of the Advent’s portfolio company, Pheno Therapeutics, which is a spin-off from Edinburgh University.