The critical challenge of gene therapy lies in delivering gene editing agents. Compared with DNA, while RNA is less stable and more accessible to degrade, it comes with the benefit of lower off-target effects since permanent insertion is not involved. This review focuses on mRNA-based delivery of gene editing agents, highlighting novel mRNA delivery systems. To provide context, a comparison is made between three main gene editing agents: programmable nucleases, base editors, and prime editors. The potential of Cas\pi and transposons is also discussed in this review. Additionally, a summary of four main barriers to mRNA-based in vivo delivery is provided. Furthermore, this review detailedly introduced different delivery systems, both viral (lentivirus) and non-viral vectors (genome editing via oviductal nucleic acids delivery, lipid nanoparticles, polymer-based nanoparticles, virus-like-particles, extracellular vesicles, and migrasome). Each delivery strategy is assessed by comparing its advantages and disadvantages to offer a comprehensive and objective overview of the delivery system. Moreover, we emphasized the vital role of the protein corona as a critical regulator for nanodelivery. Ultimately, we concluded the challenges of mRNA-based gene editing strategies (RNA stability, targeting, potential immunogenicity, cytotoxicity, heterogeneity, and rational design). The purpose of this review is to guide further research and provide a comprehensive analysis of mRNA-based in vivo delivery of gene editing agents in this promising field.

Nanocatalytic medicine triggering in situ catalytic reactions has been considered as a promising strategy for tumor-selective therapeutics. However, the targeted distribution of nanocatalysts was still low, considering the absence of targeting propulsion capability. Here, encouraged by the fast-developing controllable microrobotics for targeting delivery, a sunflower-like nanocatalytic active swarm (SNCAS) controlled by a three-dimensional (3D) magnetic field was proposed for synergistic tumor-selective and magnetic-actively tumor-targeting therapeutics. Furthermore, a patient-derived renal cancer cell 3D organoid was utilized for the verification of the effective tumor therapeutic outcomes. Under the targeted control of 3D magnetic field, the multiple cascade catalytic efficiency of SNCAS based on Fenton reaction was evaluated, resulting in efficient tumor cell apoptosis and death. For the patient-derived organoid treatment, the SNCAS presented significant lethality toward 3D organoid structure to induce cell apoptosis with the collapse of organoid morphology. The targeting efficiency was further enhanced under the magnetic-controllable of SNCAS. Overall, empowered by the magnetic control technology, the synergistic therapeutic strategy based on controllable swarm combined active targeting and tumor-specific catalytic nanomedicine has provided a novel way for advanced cancer therapy. Meanwhile, 3D patient-derived organoids were proved as a powerful tool for the effectiveness verification of nanocatalytic medicine.