Sanofi’s mRNA CAR-T Shows Tumor Suppression With Under 5% Liver Uptake
Sanofi’s preclinical mRNA CAR-T platform showed tumor suppression with under 5% liver uptake and transient CAR expression persisting several days in mouse models. The approach builds on Sanofi’s $3.2bn Translate Bio and $470m Tidal acquisitions for lipid nanoparticle delivery, targeting a $23.6bn CAR-T market by 2031.
1. mRNA CAR-T Platform Development
Sanofi’s in vivo mRNA CAR-T platform reengineers T cells within the body using lipid nanoparticles that deliver mRNA instructions for CAR production, bypassing weeks-long ex vivo manufacturing. The non-viral approach enables transient CAR expression, allowing repeat dosing and eliminating insertional mutagenesis risks.
2. Strategic Acquisitions Fuel Technology
Sanofi acquired Translate Bio in August 2021 for $3.2bn to gain LNP capabilities and Tidal Therapeutics in April 2021 for $470m to leverage VHH nanobody targeting of CD8 T cells. These purchases enhance transfection efficiency and selective tumor targeting in the in vivo platform.
3. Preclinical Efficacy and Safety
In mouse models, the lead LN15 construct encoded a CD22-targeting CAR and achieved significant tumor suppression with less than 5% liver uptake and CAR expression persisting several days. Safety assessments focus on LNP-related inflammation and cytokine release risks while monitoring efficacy of repeated dosing.
4. Clinical and Market Outlook
Upcoming clinical trials must assess remission durability compared to viral and autologous CAR-Ts and evaluate anti-drug immune responses. A successful in vivo mRNA CAR-T could reduce costs and manufacturing times, entering earlier treatment lines and addressing a CAR-T market forecasted to grow from $5bn in 2024 to $23.6bn by 2031.