Carbon-based nanomaterials in gene therapy

Gene therapy is a promising therapeutic approach to treating different diseases; however, the lack of platforms that can safely and efficiently carry desired genes to the targeted cells/tissues/organs hinders its translational and clinical applications. The use of (bio)nanomaterials to deliver the gene of interest to the targeted region has revolutionized the field of gene therapy. Among different biomaterials, carbon-based materials have been used as promising carriers to deliver genes. This review paper aims to cover applications of carbon-based nanomaterials (CbNMs), including carbon nanotubes, carbon dots, fullerene, nano-diamonds, and graphene in gene therapy. Gene therapy methods include gene augmentation (adding a new protein-coding gene), gene silencing (preventing the expression of a specific gene), suicide gene therapy, gene editing tools (such as CRISPR), and plant genetic engineering. The current review commences with a brief introduction to carbon structures, gene therapy, non-viral vectors, their ongoing challenges, and several strategies to overcome the barriers. It follows by explaining surface functionalization techniques to conjugate various nucleic acids into carbon-based nanostructures and enhance their transfection rate. Moreover, the most recent advances in different theranostic strategies have been elaborated, such as carbon dots to deliver nucleic acids and track their path. Furthermore, smart stimulus-responsive nanosystems, which are responsive to internal/external stimuli such as changes in pH, enzyme activity, reactive oxygen species (internal cues) or temperature, and light (external stimuli), will be discussed. Finally, the limitations and challenges of utilizing carbon-based materials and the advantage of having a comprehensive outlook on gene therapy will be provided while focusing on future perspectives toward more translatable gene therapy.