M6A-Modified Nucleotide Bases Improve Translation of In Vitro-Transcribed Chimeric Antigen Receptor (CAR) mRNA in T Cells.

ABSTRACT: Lentiviral transduction remains the gold standard in adoptive modified cellular therapy, such as CAR-T; however, genome integration is not always desirable, such as when treating non-fatal autoimmune disease or for additional editing steps using CRISPR to produce allogeneic CAR-modified cells. Delivering in vitro-transcribed (IVT) mRNA represents an alternative solution but the labile nature of mRNA has led to efforts to improve half-life and translation efficiencies using a range of approaches including chemical and structural modifications. In this study, we explore the role of N⁶-methyladenosine (m6A) in a CD19-CAR sequence when delivered to T cells as an IVT mRNA. In silico analysis predicted the presence of four m6A consensus (DRACH) motifs in the CAR coding sequence and tr

SUBMITTER: Lao N 

PROVIDER: S-EPMC12841529 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature