Genomic Medicine Unit: Overcoming Gene Therapy’s Greatest Challenges

At the heart of Sanofi's progress is the Genomic Medicine Unit (GMU), a team purpose-built to drive broad impact across Sanofi’s therapeutic areas. The GMU brings together expertise from diverse fields, including platform development, translational science, and manufacturing, to efficiently bring new gene therapies to patients.

"We set up the GMU to break down traditional barriers between research and real-world application," Christian explains. "Our goal is to ensure that innovative ideas become therapies that have the potential to change lives."

Sanofi’s investment in the GMU is a commitment to pushing the boundaries of genomic medicine, building advanced technology platforms, and nurturing future generations of talent. This holistic approach ensures that we remain at the forefront of next-generation gene therapies.

Gene therapy has traditionally focused on rare, single gene (monogenic) disorders. Sanofi is now building on these innovations to tackle more common immune-mediated diseases including systemic autoimmune diseases, and inflammatory conditions such as those afflicting the eyes and joints. These diseases are also known as multifactorial disorders and although more common, they are generally considered more complex than monogenic disorders as they are not confined to any specific pattern of single gene inheritance and are likely to be caused when multiple genes come together, along with the effects of environmental factors.

One of gene therapy’s greatest promises is also its biggest challenge: making sure treatments reach exactly the right cells in the right places while avoiding the body’s immune defenses. Sanofi has developed a comprehensive approach that tackles both delivery precision and immune acceptance—designed to avoid eliciting an unwanted immune response—through two complementary platform technologies.

Viral vectors are used across various applications to deliver genetic material into cells, the major applications being in gene therapy and vaccine development. Viruses are useful delivery tools, owing to their efficiency in locating and entering target cells. In addition, they are generally well tolerated to use, because all viral genes are taken out and the remaining vector is then modified to transport and deliver only the specific genetic material of interest. In many instances, once the virus has delivered the genetic material to the targeted cells, the cells are manipulated to express genes that have potential therapeutic effects. For chronic conditions, Sanofi leverages adeno-associated virus (AAV) vectors. Known for their low immunogenicity and ability to integrate into the host genome, making them suitable for long-term gene expression, these engineered vectors are used to deliver therapeutic DNA into target cells, effectively turning them into factories that continuously produce healthy proteins where they’re needed most, allowing the cell to begin fighting the disease.

This is particularly powerful for hard-to-reach areas like the eyes. In age-related macular degeneration, for example, AAV vectors can engineer retinal ganglion cells at the back of the eye to continuously produce therapeutic antibodies, potentially reducing or eliminating the need for frequent, invasive eye injections. But reaching these locations while avoiding immune rejection requires advanced engineering.

Using AI, Sanofi designs novel AAV capsids (the protein shells surrounding viral DNA), structures the body hasn’t encountered before. "We've discovered a whole new class of AAV capsids," notes Christian. “These are designed to fly under the radar of the immune system, opening up gene therapy to patients who might be otherwise excluded due to pre-existing immunity.”

In conditions like osteoarthritis, where joint cells could be prompted to produce anti-inflammatory or tissue repair proteins directly at the source of damage, novel capsids and immune-modulation strategies could also unlock the ability to repeat treatments if needed and give physicians greater flexibility in managing complex conditions while not having to exclude patients with preexisting immunity against the vectors.

While viral vectors excel at long-term payload production, some conditions benefit from more flexible approaches. When a temporary or repeatable intervention is needed, Sanofi turns to non-viral delivery systems. Lipid nanoparticles loaded with mRNA are coated with targeting antibodies, guiding them precisely to desired cells. Once delivered, the mRNA instructs cells to produce therapeutic proteins for a limited time making this method of delivery ideal for situations requiring adjustable or temporary effects.

One promising avenue is in vivo CAR-T cell therapy for autoimmune diseases. By programming immune cells inside the body to temporarily target disease-causing B cells, Sanofi aims to create more manageable therapies with an acceptable safety profile compared to traditional CAR-T approaches.

In a groundbreaking advancement, Sanofi's GMU is developing a novel approach to treat blood disorders like sickle cell disease through in vivo gene editing. Traditional gene therapy for these conditions requires extracting patients' stem cells, modifying them in a lab, and re-transplanting them—a complex and costly process requiring chemotherapy. The GMU's innovative solution uses lipid nanoparticles (LNPs) to deliver gene editing tools directly to blood stem cells in the bone marrow.

"This approach could transform treatment accessibility," explains Christian Mueller. "By eliminating the need to harvest stem cells and use chemotherapy conditioning, we are aiming to make gene therapy more simple and generally better tolerated than traditional genomic medicine treatments and available to many more patients."

The technology uses specially designed LNPs that efficiently target bone marrow stem cells after a simple intravenous injection. These nanoparticles carry mRNA encoding precise gene editing tools that can reactivate fetal hemoglobin production—a natural solution for sickle cell disease. Early research is promising, potentially offering a one-time treatment option that avoids the complications of current approaches.

Sanofi’s integrated strategy aims to develop sophisticated combination therapies from a single administration that are more effective than previous medications, with an acceptable safety profile, and potentially accessible to more patients than before. Sanofi is also looking beyond current gene therapy methods to develop treatments that are not only effective but also flexible and patient friendly. Imagine a gene therapy that can be switched on or off as needed. We’re exploring solutions activated by an oral medication, giving patients more control over their care.

"We’re building for the future," adds Christian. "Our goal is to develop therapies that are adaptable to patient needs and can evolve as science advances."

As gene therapy moves from concept to reality, Sanofi's integrated approach represents a major step forward as we look to fundamentally transform treatment paradigms. By focusing on long-term solutions and addressing root causes, we aim to replace lifelong medication regimens with one-time or controllable interventions.

"Genomic medicine is no longer experimental,” Christian concludes. “We’re not just exploring possibilities; we’re making them a reality. Taking genomic medicine out of its rare disease incubator and making it a cornerstone of modern therapeutics is the future we’re building now.”

For Sanofi, this is medicine at its purest: targeting the fundamental drivers of disease with precision and purpose.