Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS). Epstein-Barr virus (EBV)-induced B-cell overactivation could lead to inflammatory injury to the CNS, which is thought to underlie the initiation and progression of MS. To specifically eradicate these B cells, we report in situ EBNA1-specific chimeric antigen receptor (CAR)-T cells that were transiently programmed with circular RNA (circRNA)-laden CD7-targeted lipid nanoparticles (CD7-LNP). We demonstrate that systematic injection of CD7-LNP can efficiently introduce CAR circRNA to T lymphocytes and yield in vivo CAR-T cells. These in situ CAR-T cells were able to specifically clear EBNA1-specific B cells and significantly mitigate the progression of MS in a MS mouse model. Thus, in situ generation of EBNA1-specific CAR-T cells hold promise as a therapeutic strategy for MS that avoids the risks of general immunosuppression, and warrant further clinical trials.

Immunoengineering  /  CNS  /  Autoimmune disease  /  B cell  /  CAR-T  /  Lipid nanoparticles  /  Multiple sclerosis  /  EAE