Progress and prospect of minicircle as a minimized non-viral DNA vector in gene therapy and regenerative medicine

The ideal and reliable genetic treatment of human diseases relies on the use of an effective vector that does not trigger serious side effects such as immunogenicity and genotoxicity. In recent years, non-viral DNA vectors have gained significant attention due to their low cytotoxicity and minimal immune responses. Minicircles are small episomal supercoiled non-viral DNA vectors derived from conventional plasmids through in vivo recombination in bacterial cells. Numerous evidences have shown promising results in the diagnostic and therapeutic applications of minicircles due to their unique features such as small size and high ectopic expression with lower side effects. Extensive studies have shown that these minimized DNA vectors can be a superior alternative to other vectors, overcoming their technical drawbacks and clinical limitations. Based on these impressive outcomes, minicircles have remarkable potential for clinical translation in the near future. In this review, we present the characteristics, production method, advantages, and disadvantages of these vectors. We also summarize key studies that highlight the diverse and promising applications of minicircle technology as an effective tool in non-viral gene therapy and regenerative medicine.