Orléans Lab Pioneers mRNA + Ultrasound 'Bunker-Buster' Strategy Against Pancreatic Cancer

Researchers at INSERM's ART laboratory in Orléans are exploring new uses for messenger RNA (mRNA) — best known from Covid-19 vaccines — to develop therapies against aggressive cancers, with a particular focus on pancreatic cancer.

Messenger RNA molecules carry instructions from DNA that tell cells how to build specific proteins. "For cancer, this message will stimulate the patient's capacity to effectively combat tumours," said Dimitri Szymczak, project manager at the ART lab.

Although mRNA was discovered in the 1960s, it gained global prominence during the Covid-19 pandemic when scientists used it to accelerate vaccine development — an advance recognized by the 2023 Nobel Prize in Medicine. Today, most research is focused on cancer vaccines, but mRNA has many other potential applications, including boosting immunity, replacing malfunctioning cellular functions, targeting rare genetic disorders and treating allergies, according to ART lab head Chantal Pichon.

Testing and production innovations

At the ART lab, teams are designing and testing a variety of mRNA constructs on cells to confirm they are non-toxic and effective. Pichon notes there are more than 200 mRNA clinical trials worldwide run by both established pharmaceutical companies and startups.

Many mRNA products are synthesized in vitro (in test tubes) using methods that can be costly and are often covered by patents. To reduce cost, some researchers at the lab are experimenting with producing RNA inside yeast — a biological manufacturing route that could potentially cut production costs by 10 to 50 times. These yeast-derived RNAs still require rigorous purification and quality-control testing to meet pharmaceutical standards.

Combining mRNA with ultrasound: a 'bunker-buster' approach

One team at the lab is targeting pancreatic cancer, a disease with a very low survival rate. "Survival has increased only modestly — from about 5% in 2000 to roughly 10% today," said ART gastroenterologist Birane Beye, underscoring the need for new strategies beyond conventional chemotherapy and immunotherapy.

To overcome the tumour's dense protective barrier, researchers are testing a combined approach that uses powerful focused ultrasound together with an mRNA vaccine. First, ultrasound generates microscopic gas bubbles inside the tissue. When these bubbles collapse, they disrupt the tumour's surrounding barrier — a structure likened to a "bunker" — creating openings that may allow an mRNA vaccine to penetrate and train immune cells to attack the cancer.

Early laboratory and preclinical work suggests ultrasound can be safely applied to the pancreas and can enhance the effectiveness of standard treatments. The team now aims to translate these findings into clinical studies to determine whether the combination can meaningfully improve survival for pancreatic cancer patients.

Outlook

The ART lab's work reflects a broader push to expand mRNA technology beyond infectious-disease vaccines. If successful, innovations in production and delivery — including yeast manufacturing and ultrasound-assisted delivery — could make mRNA therapies more accessible and effective against cancers that have resisted current treatments.

Note: Researchers emphasize that these are early-stage efforts; rigorous clinical testing will be required to confirm safety and benefit for patients.