Tissue Tension and Strain as Indicators of Suction‐mediated Cutaneous DNA Transfection: A Parametric Study

• Published in: Advanced therapeutics Vol. 7; no. 6
• Main Authors: Jhumur, Nandita Chakrabarty, Lallow, Emran O., Nachtigal, Catherine J., Yeo, Dahee, Kwon, Ijoo, Park, Young K., Roberts, Christine C., Zahn, Jeffrey D., Shreiber, David I., Shan, Jerry W., Singer, Jonathan P., Maslow, Joel N., Lin, Hao
• Format: Journal Article
• Language: English
• Published: 01.06.2024
• Subjects: GFP expression; suction; tissue strain; tissue tension; transfection
• ISSN: 2366-3987; 2366-3987
• DOI: 10.1002/adtp.202400055

Cutaneous suction‐based transfection is a recently developed technique that is painless and simple‐to‐use for the delivery of DNA for nucleic‐acid‐based vaccines. The technique promises high efficiency for both antigen expression and immunogenicity as demonstrated in both animal studies and human clinical trials. To realize this promise, a parametric study and systematic evaluation of the efficacy of cutaneous suction as a transfection method is performed. Using Green Fluorescent Protein (GFP) plasmid expression as a transfection reporter in a rat model, the expression level as a function of both suction nozzle size and suction pressure is quantified. A numerical model is employed to compute skin deformation in terms of strain, which is used to correlate with GFP expression. Based on these results, two quantities, integrated total strain and tissue tension, are proposed as indicators of expression level that can be used to guide protocol development and optimization. These indicators are also discussed in relation to possible cellular uptake mechanisms. Cutaneous suction application following an intradermal (ID) DNA injection promotes nucleic‐acid‐based vaccine delivery and transfection. A parametric study of suction‐based transfection is performed using GFP plasmid in rat skin varying both suction‐nozzle size and suction pressure. Integrated total strain calculated from numerical simulation and tissue tension are found to correlate with GFP expression level.