New system for therapeutic gene delivery increases transgene expression up to 100-fold
New Rochelle, NY, Jan. 27, 2017 — Advanced engineering of a mini-intronic plasmid (MIP) system designed to carry a therapeutic gene can significantly enhance the expression of the transgene delivered using an adeno-associated viral (AAV) 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. The article is available free on the Human Gene Therapy website until February 28, 2017 .
Authors Jiamiao Lu, Feijie Zhang, and Mark Kay, Stanford University, Palo Alto, CA, and James Williams and Jeremy Luke, Nature Technology Corp., Lincoln, NE, describe the modified MIP expression system in the article entitled "A 5' Non-coding Exon Containing Engineered Intron Enhances Transgene Expression from Recombinant AAV Vectors in vivo." The researchers discuss the potential implications of enhanced transgene expression on the doses needed to achieve a therapeutic response and the flexibility the small intronic sequences offer, allowing them to be used in both DNA plasmids and viral delivery vectors.
"Careful observation of the expression characteristics of different vector designs sometimes leads to unexpected findings," says Editor-in-Chief Terence R. Flotte, MD, Celia and Isaac Haidak Professor of Medical Education and Dean, Provost, and Executive Deputy Chancellor, University of Massachusetts Medical School, Worcester, MA. "In this case, the authors found that a very substantial increase in the amount of transgene expression (up to 100-fold) could be achieved from rAAV vectors by including essential bacterial plasmid elements in an upstream intron. This could present substantial advantages for future in vivo gene therapy."
About the Journal
Human Gene Therapy, the Official Journal of the European Society of Gene and Cell Therapy, British Society for Gene and Cell Therapy, French Society of Cell and Gene Therapy, German Society of Gene Therapy, and five other gene therapy societies, is an authoritative peer-reviewed journal published monthly in print and online. Led by Editor-in-Chief Terence R. Flotte, MD, Celia and Isaac Haidak Professor of Medical Education and Dean, Provost, and Executive Deputy Chancellor, University of Massachusetts Medical School, Human Gene Therapy presents reports on the transfer and expression of genes in mammals, including humans. Related topics include improvements in vector development, delivery systems, and animal models, particularly in the areas of cancer, heart disease, viral disease, genetic disease, and neurological disease, as well as ethical, legal, and regulatory issues related to the gene transfer in humans. Its companion journals, Human Gene Therapy Methods, published bimonthly and focused on the application of gene therapy to product testing and development, and Human Gene Therapy Clinical Development, published quarterly, features data relevant to the regulatory review and commercial development of cell and gene therapy products. Tables of contents for all three publications and a free sample issue may be viewed on the Human Gene Therapy website.
About the Publisher
Mary Ann Liebert, Inc., publishers is a privately held, fully integrated media company known for establishing authoritative peer-reviewed journals in many promising areas of science and biomedical research, including Nucleic Acid Therapeutics, Tissue Engineering, Stem Cells and Development, and Cellular Reprogramming. Its biotechnology trade magazine, GEN (Genetic Engineering & Biotechnology News), was the first in its field and is today the industry's most widely read publication worldwide. A complete list of the firm's 80 journals, books, and newsmagazines is available on the Mary Ann Liebert, Inc., publishers website.