MXene and 2D Transition Metal Carbide/Nitride Nanocarriers for Gene-Editing and mRNA Therapeutics: Design Principles, Biosafety Challenges, and Translational Roadmap

Gene editing (e.g., CRISPR-Cas systems) and mRNA therapeutics hold great promise for addressing genetic and acquired diseases, but their clinical translation is impeded by delivery challenges including cargo instability, immunogenicity, off-target effects, and inadequate cellular uptake. MXenes and other two-dimensional (2D) transition metal carbides/nitrides have emerged as versatile nanomaterials with tunable surface chemistry, high surface area, and potential for functional modification. This review critically examines recent advances (2018–2025) in MXene-based and related 2D nanocarriers for CRISPR RNP, sgRNA, and mRNA delivery, focusing on: (i) materials design (surface terminations, defect control, hybridization); (ii) cargo loading and protection strategies; (iii) cellular uptake, endosomal escape, intracellular release; (iv) in vitro and in vivo efficacy; (v) biosafety, biodegradation, and immunogenicity; (vi) manufacturing, characterization and regulatory challenges. We highlight comparative strengths and limitations relative to lipid nanoparticles (LNPs), polymeric nanocarriers, and gold nanoparticles. Finally, we propose a translational roadmap to guide future research toward clinical application. This review aims to fill a gap in the literature: there is no existing comprehensive summary focused explicitly on MXene/2D carbide/nitride nanocarriers for gene editing and mRNA therapies.