This is the present – and promise – of gene therapy. But gene-based therapy opens even more possibilities, and almost unlimited potential, beyond rare genetic disorders.
“It’s a new frontier,” says James Sabry, Global Head of Roche Pharma Partnering. “In many ways, the limitations are only what scientists can think of, and that’s really where the value of collaboration across Roche and with our current and future partners comes in.”
This mindset led to the acquisition of Spark Therapeutics, the Philadelphia-based gene therapy center of excellence within Roche.
“Imagine a world where no life is limited by genetic disease and the ambition of gene therapy to treat or possibly prevent disease is realized for the millions of people living with an inherited condition,” says Jeff Marrazzo, CEO and co-founder of Spark Therapeutics. “By addressing some diseases at a genetic level, entire lives, families and our global healthcare system could be transformed by unlocking the full potential of gene therapy.”
The next generation of pioneering medicines, with gene therapy front and centre, is blazing a path towards truly personalised global healthcare. It’s a proactive approach, strengthened by partnering and collaboration, that seeks better healthcare at a lower cost to society.
To understand gene therapy, we should start with genes. Cells are the basic units of life, and each cell contains a full set of instructions, or genes. Each gene encodes for a different protein, or the “business ends” of the cell and the regulatory instructions of when to use this gene. Cells in our body are different, and each cell uses only some of the genes based on its needs – immune cells will need genes for proteins like antibodies to fight off infections, brain cells will need the genes that encode neurotransmitters, and so on.
But sometimes our genes have a glitch in the code, either one that we inherit from our parents at birth, or one that arises within our own bodies over time, and that can cause disease, because the cells cannot work properly. In some inherited cases, the error is major, and will cause a severe disease like haemophilia or Huntington’s disease. In other cases, the differences we inherit are part of the natural variation between humans, but can increase our risk of common diseases, like heart disease or type 2 diabetes. But genes can also mutate during our lifetime, especially due to errors accrued over the lifespan, resulting in illnesses, especially cancer.
In the future, instead of a series of traditional medical treatments that only manage some diseases – or a lifetime of injections, infusions, monitoring, adjustments and ongoing doctor appointments – patients might instead receive gene therapy treatment to fix that glitch.
Learn more about genes and gene therapy in this video
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While the prospects of gene therapy are awe-inspiring, it won’t be easy or instantaneous. Before we ride off into a sunset with great therapies for genetic disease, there are challenges to overcome. Some aspects of the science behind gene therapy are uncharted; there will be stumbles, disappointments and setbacks.
Even when solutions are found in a laboratory, in the form of novel vectors or “messengers” that carry new genetic instructions to block, take down or take over for malfunctioning ones, those breakthroughs must then be meticulously translated to humans and into large-scale production processes that can repeatedly and reliably produce the same medicines in manufacturing facilities.
In some cases, the future is now. In 2019 Spark Therapeutics, located in Philadelphia, became the gene therapy center of excellence within Roche. The Roche Group’s bold commitment to gene therapy collaborations across the organisation and industry are a stake in the ground: the possibility and potential of using genes to treat or prevent disease now and in the future is one clear path to where the Roche Group and healthcare are headed.
Oftentimes, the many remaining challenges can be solved by bringing together different scientists and approaches in a partnership. For example, Roche entered into two collaborations in 2020 that focus on solving two parts of the puzzle. Roche and Spark Therapeutics are working with Dyno Therapeutics to engineer optimised viral capsids (think of tiny packages that protect, transport and deliver genetic solutions,) with the help of machine learning applied to biology. And a partnership with CEVEC Pharmaceuticals will leverage their expertise in high-performance viral vector production. Viral vectors are tools that deliver genetic material into cells, and this partnership could enable large-scale biopharmaceutical manufacturing of those vectors.
“I believe that within 20 or 30 years from now, gene therapy will represent the most important class of pioneering medicines in our industry,” James says. “The reason for that is clear: if you can go in and do genetic surgery – by removing malfunctioning or abnormally regulated genes and replacing them with genes that are normally regulated – then you can get to the basis of what causes disease and fix it. It's version 1.0 right now for gene therapy, but we're very excited about the future, and our partnership with trailblazing companies like Spark make this vision a reality.”
Already today, there is initial evidence that gene therapy could change the lives of patients with certain diseases by introducing a working gene to step in and do the job of a malfunctioning one. But in versions 2.0 or 3.0, gene therapy would involve taking out one gene and replacing it with another, like surgery at a genetic level, or by adding a new gene to produce a protein that is therapeutic, like a vectorised antibody medicine against a target that causes disease.
Spark Therapeutics was the first company in the U.S. to launch a gene therapy, backed by its robust research, commercial and manufacturing capabilities. After a long courtship, Roche and Spark aligned their
Ultimately, the future of medicine will be a combination of complementary approaches, Federico says, including small molecules, large molecules, and programmable therapies that include gene therapy, cell therapy, bacterial therapies and RNA-based therapies. Spark Therapeutics is an integral part of that within Roche.
“There was enormous excitement in the company after the acquisition,” Federico says. “We're still working hard to develop gene therapies, but we are also collaborating more and more with our colleagues across Roche. This is fantastic, because it creates novel opportunities to develop life-changing medicines. Combining capabilities is a great way to speed up the development of new therapies to bring to patients. That's the part of my job that I love, and that is what brings me to work every day.”
Our scientists share their vision and hope for the unlimited possibilities and potential of gene therapy
“With Huntington’s disease, for instance, gene therapy might lead to faster and wider access to the target – the root cause of that specific disease. And that speed and accuracy in getting to the target might result in slowing the disease. The potential of slowing a disease early, or before it even begins, is indeed exciting.”
“Gene therapy is a ‘programmable’ therapy that allows us to rewrite the cellular program. For this we need great targets, and a great understanding of which cells in which tissue to target in a disease. The scientists at Genentech Research and Early Development (gRED) leverage strengths across all these areas, and powerful computational approaches like machine learning to help us get there faster.”
“Gene therapy is a cornerstone of our vision for the future, and it creates almost unlimited possibilities for our scientists to deliver new transformative medicines. Combining our strengths with partners and collaborators who share our vision and passion of targeting disease at a genetic level, we will hopefully change healthcare – and global health – for the better.”
"To advance science we need to think about the impossible. By connecting the brightest minds in Roche and in the biotechs we partner with, we are continuously pushing the boundaries to find innovative solutions to the challenges we need to overcome to hopefully make gene therapy a reality for a broad range of patients."
“The life-changing goal with gene therapies is to create a single therapeutic intervention that is curative. That is absolutely transformative when it comes to the potential impact on the lives of patients. Emerging data on the long-term safety and efficacy of gene therapy patients is promising, as it shows that it is possible to achieve a durable effect over time. The potential of curing and preventing disease, versus treating or maintenance, is our passion and what drives us forward.”
Today’s healthcare uses traditional drugs that target proteins to manage or treat disease. But gene therapy impacts the genes that code the proteins, and in this way uses genes to treat or someday even prevent disease.
Genes can be delivered to cells in different ways. From the beginning, Spark Therapeutics has focused on adeno-associated virus (AAV) vectors, which are derived from a virus found in nature. Viral vectors harness the innate ability of a virus to enter cells, carrying the therapeutic gene with them. AAVs are an attractive option as a “messenger” to deliver genes, as they are considered safe, stable and keep cells intact.
One day, gene therapy could become a common approach to use the human body itself as a manufacturing site for therapeutic proteins that we design. Instead of companies like Roche manufacturing proteins in a large-scale, high-tech production plant, protein therapies would go hyper-local and could be “manufactured” in your liver, for instance, or in the glial cells in your brain.
“What gene therapy allows us to do, potentially, is to use the human body, as our own specialised biofactory – that is, we can use programmed genes for the production of protein and antibody treatments against chronic diseases,” says Sylke Poehling, Senior Vice President, Global Head, Therapeutic Modalities, Roche Pharma Research & Early Development. “These are the ways we're thinking about how we can all come together to complement and push the boundaries of what we're currently doing.”
Beyond the push toward next-level science, pioneering medicines also require a shift in mindset, in terms of costs, to move from reactive healthcare solutions to a proactive one, like gene therapy. Most health systems today diagnose and treat patients in later stages of disease and are built on treatments for chronic conditions.
“This happens if you have a coronary artery bypass graft, or have your appendix removed via surgery, but in the future it will be genetic surgery and it can happen earlier,” says William Pao, Global Head, Roche Pharma Research & Early Development. “That expands what we think of as a drug, and has huge implications for the healthcare system in terms of ease of use and access to the therapy, and also in terms of economics of the therapy.”
The cost of healthcare – not only financial but also in quality of life for the patient – is traditionally borne over years (sometimes decades) of treatments or anatomic surgery. Gene therapy can potentially flip that script, putting the cost of diagnosis, cure or prevention up-front, as an investment in fewer chronic diseases and better quality of life in the future. This will require collaboration with health systems across the globe to allow for innovative payment models that ensure the promising science of gene therapy can ultimately reach patients.
"We envision a world where no life is limited by genetic disease, and reaching that point requires us to unlock the full potential of gene therapy,” Jeff says.
“To do that, we're exploring ways to broaden our current pipeline, which is focused on monogenic diseases – diseases caused by a variation in a single gene – and on three main target tissues: the eye, the liver and the central nervous system,” Federico says.
The goal for the future? Expansion not only to other therapeutic areas, but also to more complex diseases, where multiple genes each contribute a small portion of risk, based on variants common in the human population. The bottom line, Federico says, is to bring more gene therapies to more patients to transform clinical outcomes, and ultimately transform healthcare for the better.
Through an integrated gene therapy platform,
Meet some of our partners who share our vision for transforming healthcare through gene therapy.
Roche is committed to driving groundbreaking scientific and technological advances that have the potential to transform the lives of patients worldwide. But we
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