Abstract
Effective transfection of genetic molecules such as DNA usually relies on vectors that can reversibly uptake and release these molecules, and protect them from digestion by nuclease. Non-viral vectors meeting these requirements are rare due to the lack of specific interactions with DNA. Here, we design a series of four isoreticular metal-organic frameworks (Ni-IRMOF-74-II to -V) with progressively tuned pore size from 2.2 to 4.2 nm to precisely include single-stranded DNA (ssDNA, 11–53 nt), and to achieve reversible interaction between MOFs and ssDNA. The entire nucleic acid chain is completely confined inside the pores providing excellent protection, and the geometric distribution of the confined ssDNA is visualized by X-ray diffraction. Two MOFs in this series exhibit excellent transfection efficiency in mammalian immune cells, 92% in the primary mouse immune cells (CD4+ T cell) and 30% in human immune cells (THP-1 cell), unrivaled by the commercialized agents (Lipo and Neofect).
Highlights
Effective transfection of genetic molecules such as DNA usually relies on vectors that can reversibly uptake and release these molecules, and protect them from digestion by nuclease
The precise control of pore geometry and strength of interaction with guest molecules were achieved by the design and synthesis of a series of metal-organic frameworks (MOFs) with the same topology but progressively increasing pore sizes (Fig. 1 and Supplementary Figure 1)
The gradual pore size expansion was implemented by inserting multiple phenylene units into the original 2,5-dioxidoterephthalate linker to prepare organic linkers of different length (Fig. 1a)
Summary
Effective transfection of genetic molecules such as DNA usually relies on vectors that can reversibly uptake and release these molecules, and protect them from digestion by nuclease. We show that single-stranded DNA (ssDNA) of different length (11, 22, 33, and 53 nucleotides) can be selectively bound into a series of MOFs featuring pore sizes from 2.2 to 4.2 nm with two members exhibiting optimal binding strength to allow precise release of ssDNA into a wide range of cell types including primary mouse and human immune cells, with high transfection efficiency. Such performance is unrivaled by the commercialized non-viral vectors including Neofect and Lipo. This work presents a unique method of regulation on the interaction through tuning pore sizes in a precise manner
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