Hello!
We are using LNP to deliver circular mRNA into T cells. However, compared with linear mRNA, the transfection efficiency and protein expression duration are similar. Are LNP generation or transfection protocols different for circular mRNA delivery compared to linear mRNA. Thank you for your suggestion.
I am not an expert in this field, but I am very interested and have researched to find an answer. I received some assistance from tlooto.com for this response. Could you please review the response below to see if it is correct?
For transfecting circular mRNA into T cells using lipid nanoparticles (LNPs), it is essential to consider optimization beyond standard protocols used for linear mRNA. Circular mRNA’s unique structure might require adjustments in lipid composition, as specific ionizable lipids, phospholipids, and polyethylene glycol (PEG)-conjugated lipids can significantly improve delivery efficiency [1][2][3]. Additionally, the encapsulation process and LNP stability might need fine-tuning to enhance mRNA uptake and expression [4][5][6]. Experimenting with different lipid formulations, such as incorporating β-sitosterol or adjusting DOPE content, may also yield better transfection outcomes and prolonged protein expression [6][7][8].
Reference
[1] Billingsley, M. M., Singh, N., Ravikumar, P., Zhang, R., June, C., & Mitchell, M. J. (2020). Ionizable Lipid Nanoparticle Mediated mRNA Delivery for Human CAR T Cell Engineering.. Nano letters.
[2] Billingsley, M. M., Hamilton, A. G., Mai, D., Patel, S. K., Swingle, K., Sheppard, N., June, C., & Mitchell, M. J. (2021). Orthogonal Design of Experiments for Optimization of Lipid Nanoparticles for mRNA Engineering of CAR T Cells.. Nano letters.
[3] Zong, Y., Lin, Y., Wei, T., & Cheng, Q. (2023). Lipid Nanoparticle (LNP) Enables mRNA Delivery for Cancer Therapy. Advanced Materials, 35.
[4] Ye, Z., Chen, J., Zhao, X., Li, Y., Harmon, J., Huang, C., Chen, J., & Xu, Q. (2022). In Vitro Engineering Chimeric Antigen Receptor Macrophages and T Cells by Lipid Nanoparticle-Mediated mRNA Delivery.. ACS biomaterials science & engineering.
[5] Zeng, Y., Escalona-Rayo, O., Knol, R. A., Kros, A., & Slütter, B. (2022). Lipid nanoparticle-based mRNA candidates elicit potent T cell responses.. Biomaterials science.
[6] Tanaka, H., Miyama, R., Sakurai, Y., Tamagawa, S., Nakai, Y., Tange, K., Yoshioka, H., & Akita, H. (2021). Improvement of mRNA Delivery Efficiency to a T Cell Line by Modulating PEG-Lipid Content and Phospholipid Components of Lipid Nanoparticles. Pharmaceutics, 13.
[7] Thatte, A. S., Hamilton, A. G., Nachod, B. E., Mukalel, A. J., Billingsley, M. M., Palanki, R., Swingle, K., & Mitchell, M. J. (2023). mRNA Lipid Nanoparticles for Ex Vivo Engineering of Immunosuppressive T Cells for Autoimmunity Therapies.. Nano letters.
[8] Robinson, E. R., Kare, A., Kheirolomoom, A., Inayathullah, M., Tumbale, S. K., Wu, B., Raie, M., Seo, J., Salazar, F., Paulmurugan, R., Wu, A. M., & Ferrara, K. W. (2022). Abstract 5372: CD3 and CD8 targeting of ionizable lipid nanoparticles for in vivo mRNA delivery to T cells. Cancer Research.
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