A critical view of silk fibroin for non-viral gene therapy

Exogenous genes are inserted into target cells during gene therapy in order to compensate or rectify disorders brought on by faulty or aberrant genes. However, gene therapy is still in its early stages because of its unsatisfactory therapeutic effects which are mainly due to low transfection efficiency of vectors, high toxicity, and poor target specificity. A natural polymer with numerous bioactive sites, good mechanical qualities, biodegradability, biocompatibility, and processability called silk fibroin has gained attention as a possible gene therapy vector. Using silk fibroin as a gene vector can reduce cell toxicity, extend the duration of gene expression, and allow further release even in the bloodstream, thereby expanding its therapeutic scope. This review outlines the advancements made with regard to gene delivery methods based on silk fibroin materials in the fields of malignant tumors, bone tissue regeneration, neural tissue, and vascular tissue engineering. Silk fibroin exhibits remarkable repair and therapeutic effects in gene therapy and can be employed in numerous forms, such as a vector (nanoparticles, microcapsules) or a matrix (hydrogel, scaffold) for gene delivery.