The route to enhanced gene therapies

What are the main current trends in gene therapy?

In recent years, the gene therapy landscape has undergone significant transformation, with a surge in gene therapies advancing through clinical development and gaining regulatory approvals. This progress underscores the potential of gene therapy to revolutionise medicine by addressing the root causes of genetic disorders.

The good news is that we are starting to see this happen, particularly in the rare disease space where many diseases have a genetic cause. With some of the gene therapies now available, we are observing disease remission and increased life expectancy, offering patients and their families the hope they have long sought since diagnosis.

Moreover, we are witnessing a rising trend of drug developers focusing on diseases with high unmet needs, especially those that are terminal or are aggressively progressive, particularly where other treatment options are either inadequate or non-existent. In neurology, for example, UCB is targeting severe neurological and neurodegenerative conditions where gene therapies have the potential to be truly transformative, relieving patients of long-term treatment burdens and significantly improving their quality of life.

There is also a growing focus on improving delivery mechanisms, with delivery remaining a major obstacle to the adoption of gene therapies. New technologies are needed to target specific organs safely and efficiently to reduce the risk of off-target effects and enhance therapeutic efficacy.

We are seeing growing research into viral and non-viral gene delivery systems, targeted nanoparticles, biosafe carriers, and precision editing tools like CRISPR–Cas9, base editing, and prime editing which allow precise modifications directly within the genome.

What key developments in gene therapy are you most excited about? Why?

The emergence of innovative technologies that aim to address the obstacle of gene therapy delivery, such as adeno-associated virus (AAV) is of particular interest. There has been great progress in the precise delivery of gene therapies to specific target tissues or organs. At UCB, we are also investing in technologies that could enable systemic administration of gene therapies to better target the diseased tissue while sparing healthy tissue.

What modality do you think has the most promise and why?

The potential and credibility of AAV vectors immediately come to mind. Compared to other delivery technologies, AAV stands out for its proven ability to deliver payloads to target cells, favourable tolerability profile and for its durability meaning treatments have long-lasting beneficial effects.

AAV remains a cornerstone in our approach, especially as we delve into severe neurological and neuromuscular diseases, and offers benefits over existing viral and non-viral delivery methods including:

• Delivery directly to the target site is crucial for both efficacy and safety
• Superior durability, meaning long-lasting gene expression
• Flexibility for different gene therapy applications.

What should the industry prioritise to advance the gene therapy field? What are the current barriers and how could these be mitigated?

From a technology perspective, safe and efficient delivery to the right target tissue or organ is fundamental and should be prioritised because it is crucial that treatments achieve their therapeutic goals. While AAV-based approaches have been curative for some diseases, there is an opportunity for novel delivery mechanisms that offer even more precise and efficient delivery.

From a sustainability perspective, there is a need to explore how we can lower the cost of production and dose so that gene therapies are more accessible overall, and I feel that manufacturing and delivery innovations are key in the solution to this challenge.  

How can the industry advance the skills of the upcoming workforce?

Collaborations with stakeholders across the industry will encourage much-needed continued innovation in gene therapy.

To build a skilled workforce, it is important to harness the collective strength of our wider organisational networks and partnerships. The industry should actively cultivate collaborations with academic institutions and other entities to provide training and development opportunities.

Such partnerships facilitate the upskilling of the workforce and create self-sustaining ecosystems. This approach has proven both efficient and cost-effective. At UCB, we have established an initiative through our partnership with the Belgian research university KU Leuven, which is focused on building up the next generation of gene therapy researchers.

What could be the next major disruptor in the field?

While personalised medicine is key across all modalities, but for gene therapy, it comes back to delivery. If people can solve the delivery issue, this would truly disrupt the field by unlocking the full spectrum of diseases that could be targeted, including multi-organ and complex conditions beyond those that are tissue specific or genetically driven.

I feel like we have just scratched the surface with gene therapy and I am excited to see what else we can realise in the years to come.