Magnetic metal–organic frameworks as an antisense delivery platform and their performance in a cell-free protein expression system

Nanosized metal-organic frameworks (nMOF) have become one of the most promising classes of drug delivery vehicles due to their high load capacity, controllable drug release, and potential for transporting multiple payloads. Magnetic nMOFs, composed of a magnetic core and MOF coating, can further enhance their functionality through remote control using an external magnetic field. However, only a few studies have investigated the potential toxicity of magnetic nMOFs and the effects of their degradation on cellular machinery and the translation process. Here we show magnetic MOFs that: (i) regulate gene expression through antisense payload delivery; (ii) do not inhibit protein synthesis. We harness a cell-free protein system, CFPS, to investigate gene expression under more controlled conditions compared to traditional cell-based systems. Our findings demonstrate that magnetic nMOFs, with a magnetite core and a MIL-100(Fe) shell, do not inhibit protein translation upon degradation, and nMOFs loaded with antisense oligonucleotides can suppress protein translation by up to 87%. Furthermore, the magnetic nature of nMOFs ensured the fine-tuning of gene expression through remote control <i>via</i> a magnetic field without any additions to the CFPS system, thus offering an additional modality for the "on/off" control of cell-free protein synthesis. Considering the promising characteristics of nMOFs as delivery systems with minimal side effects, we anticipate their use in cutting-edge synthetic biology, biomedical applications, and the creation of the next generation of theranostic agents.