Human T cell engineering via serial delivery of mRNA encapsulated within lipid nanoparticles.

Lipid nanoparticle delivery of mRNA achieves 100% higher T cell viability and enhanced protein expression compared to electroporation in serial human T cell engineering.

• Why it matters: Efficient and safe delivery of nucleic acids to T cells is crucial for advancing cell therapies for cancer and autoimmune diseases, but current methods often reduce T cell viability and function.
• What they did: The study tested serial delivery of mRNA encapsulated in lipid nanoparticles containing DOTAP and DOPE, comparing their efficiency to standard formulations and electroporation, with a focus on primary human T cells.
• The result: DOTAP/DOPE-LNPs delivered mRNA more effectively, maintaining higher T cell viability over multiple transfections, and successfully produced functional CAR T cells, offering a promising alternative for T cell engineering.