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DNA Diffusion in Mucus: Effect of Size, Topology of DNAs, and Transfection Reagents

Hong Shen ^*, Yueyue Hu  and W. M. Saltzman ^*

^* Departments of Biomedical and Chemical Engineering, Yale University, New Haven, Connecticut

Correspondence: Address reprint requests to W. M. Saltzman, E-mail: mark.saltzman{at}yale.edu.

DNA represents a promising therapeutic and prophylactic macromolecule in treating genetic diseases, infectious diseases and cancers. The therapeutic potential of DNA is directly related to how DNA transports within the targeted tissue. In this study, fluorescence photobleaching recovery was used to examine the diffusion of plasmid DNAs with various size (2.7 8.3 kb), topology, and in the presence of transfection reagents in mucus. We observed that DNAs diffused slower when size of DNAs increased; supercoiled DNAs diffused faster than linear ones; mucus did not reduce the diffusion of linear DNAs but retarded the diffusion of supercoiled DNAs. Diffusion data were fitted to models of a polymer chain diffusing in gel systems. Diffusion of linear DNAs in mucus were better described by the Zimm model with a scaling factor of –0.8, and supercoiled DNAs showed a reptational behavior with a scaling factor of –1.3. Based on the Zimm model, the pore size of bovine mucus was estimated and agreed well with previous experimental data. In the presence of transfection reagents, e.g., liposomes, the diffusion of DNAs increased by a factor of 2 in mucus. By using bovine mucus as a model system, this work suggests that DNA size, topology, and the presence of transfection reagents may affect the diffusion of DNA in tissues, and thus the therapeutic effects of DNA.