Advanced engineering of a mini-intronic plasmid system designed to carry a therapeutic gene can significantly enhance the expression of the transgene delivered using an adeno-associated viral vector. The ability to increase transgene expression by up to 40 to 100-fold, which would reduce the cost of manufacturing and perhaps also lessen the immune response of AAV/MIP-based gene therapy, is reported in Human Gene Therapy, a peer-reviewed journal from Mary Ann Liebert, Inc., publishers.