Low-energy ion beam-assisted delivery of genetic engineering tools for gene therapy: A proof-of-concept

Gene therapy is a promising approach for treating genetic diseases by correcting mutated genes to cure or prevent various inherited and acquired conditions. This strategy relies on the integration of gene delivery systems and genetic engineering techniques. However, the efficiency and safety of each gene delivery approach are major bottlenecks hindering their practical use in medical applications. Current delivery platforms, including viral and non-viral systems, are limited by tradeoffs among transfection efficiency, cargo capacity, and cytotoxicity. Among these, low-energy ion beam-assisted gene delivery (LEIBGD) has gained attention as a potential physical transfection strategy that offers a carrier-free and potentially size-independent approach for intracellular delivery. By introducing controlled nanoscale modifications on the cell membrane, LEIBGD facilitates the entry of genetic materials while minimizing biological barriers associated with conventional methods. This proof-of-concept-oriented review constructively provides a comprehensive evolution of current genetic engineering approaches and gene delivery systems, highlighting their strengths and limitations. Particular emphasis is placed on the mechanisms, advantages, and challenges of LEIBGD. Additionally, we discuss its emerging potential for delivering next-generation genetic engineering tools, especially in sensitive systems such as induced pluripotent stem cells. Overall, LEIBGD represents an alternative platform that could help overcome existing delivery constraints and advance the future of precision gene therapy.