Minicircles: next-generation gene vectors with high potential for clinical applications

The potential of gene therapy in clinical settings relies on the effective delivery of nucleic acids to target cells or tissues. Significant progress has been made in the field using both viral and non-viral vectors as delivery mechanisms. Plasmid DNA remains a crucial starting material for both strategies. Recent regulatory requirements have necessitated the use of safe and advanced Next-Generation Gene Vectors.

Minicircles are plasmid derivatives engineered to be devoid of bacterial sequence elements, such as antibiotic resistance genes or replication origin. In addition to reducing the size compared to the original plasmid, trimming away these excess sequence enables the molecule to evade host immune responses more effectively and making it better equipped to circumvent gene silencing scenarios post-transfection.

Minicircle delivery vehicles are already used in diverse applications and proved to be advantageous over conventional plasmid DNA:

Sleeping Beauty-based transposition is being used to generate CAR-T cells, which are currently considered the most promising tool in cancer therapy. A higher transposition rate was observed when using minicircles compared to plasmids.

When used for AAV production, minicircles offer unique advantages, eliminating the possibility of backbone sequences being falsely packaged into the transfer vectors.