Metal-organic frameworks for precise inclusion of single-stranded DNA and transfection in immune cells

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).

DNAzyme‐Loaded Metal–Organic Frameworks (MOFs) for Self‐Sufficient Gene Therapy

“…A class of hybrid nanomaterials known as metal–organic frameworks (MOFs) has attracted substantial attention in gas storage and separation, selective catalysis, and drug delivery, benefiting from their high and tunable porosity, large surface area, and ease of functionalization. MOFs are also utilized as robust solid scaffolds for anchoring nucleic acids through electrostatic adsorption, covalent conjugation, or van der Waals interactions, yet they suffer from either environmental vulnerability or tedious assembly. MOFs have been introduced as robust vessels for siRNA or DNAzymes without stimuli‐responsiveness .…”

“…MOFs are also utilized as robust solid scaffolds for anchoring nucleic acids through electrostatic adsorption, covalent conjugation, or van der Waals interactions, yet they suffer from either environmental vulnerability or tedious assembly. MOFs have been introduced as robust vessels for siRNA or DNAzymes without stimuli‐responsiveness . Surface‐anchored DNAzymes have been introduced as stimuli‐responsive molecular locks or caps for programming drug release from the underlying MOFs scaffolds .…”

Design Rules for Metal‐Organic Framework Stability in High‐Pressure Hydrogen Environments

“…Magnesium‐ and nickel‐based MOF‐74 were chosen to compare the effect of metal redox activity on stability, and Ni 2 ( m ‐dobdc) was selected to examine the effect of node distortion. Other members of the isoreticular Ni‐IRMOF‐74 series were also prepared to investigate the effect of increasing pore size and volume.…”

Generation of Hierarchical Porosity in Metal–Organic Frameworks by the Modulation of Cation Valence

“…Metal–organic frameworks (MOFs), constructed via the self‐assembly of metal ions (or clusters) and organic ligands, have attracted extensive attention because of their diverse topologies, tunable functionalities, and large surface areas . These characteristics make MOFs potentially useful in various applications, such as catalysis, adsorption, and sensing . It is noticeable that most reported MOFs are microporous with pore sizes less than 2 nm, which favors the capture/separation of guests with small molecular sizes.…”