Macrophage manufacturing and engineering with 5'-Cap1 and N1-methylpseudouridine-modified mRNA.

ABSTRACT: Macrophage-based cell therapeutics is an emerging modality to treat cancer and repair tissue damage. A reproducible manufacturing and engineering process is central to fulfilling their therapeutic potential. Here, we establish a robust macrophage-manufacturing platform (Mo-Mac) and demonstrate that macrophage functionality can be enhanced by N1-methylpseudouridine (m1Ψ)-modified mRNA. Using single-cell transcriptomic analysis as an unbiased approach, we found that >90% cells in the final product were macrophages while the rest primarily comprised T cells, B cells, natural killer cells, promyelocytes, promonocytes, and hematopoietic stem cells. This analysis also guided the development of flow-cytometry strategies to assess cell compositions in the manufactured product to meet requirements

SUBMITTER: Zhang P 

PROVIDER: S-EPMC11369376 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature