Dexamethasone enhances transgene expression when administered after gene therapy

Dexamethasone, a glucocorticoid with anti-inflammatory and immunosuppressive effects, can transiently increase the expression of therapeutic genes delivered using adeno-associated virus (AAV) vectors. A new study, which showed that dexamethasone administration at a late time point could increase transgene expression from AAV9 vector transduced liver in mice, was published in the peer-reviewed journal Human Gene Therapy. Click here to read the article now.

“Corticosteroids like dexamethasone, methylprednisolone and prednisone are frequently used in AAV-based human gene therapy protocols, but the optimal timing of such therapy has not been thoroughly studied,” says Editor-in-Chief of Human Gene Therapy Terence R. Flotte, MD.  “This paper provides an interesting insight into the potential effects of short-duration steroid therapy.”

Chengwen Li, PhD and coauthors from the University of North Carolina at Chapel Hill demonstrated that the increased transgene expression was not dependent on the duration or time point of dexamethasone administration after AAV injection. The researchers did not report increased transgene expression in hemophilia dogs treated with dexamethasone after AAV gene therapy.

“These results provided valuable information to design an effective approach for application of dexamethasone in future clinical studies with AAV vector liver targeted gene therapy, such as short term and intermittent administration of steroids,” state the investigators. “This may decrease the toxicities from long term application of steroids and also avoid liver damage from high doses of AAV vector seen in clinical trials.”

About the Journal

Human Gene Therapy, the Official Journal of the European Society of Gene and Cell Therapy and eight other international gene therapy societies, was the first peer-reviewed journal in the field and provides all-inclusive access to the critical pillars of human gene therapy: research, methods, and clinical applications. The Journal is 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, and an esteemed international editorial board. Human Gene Therapy is available in print and online. Complete tables of contents and a sample issue are available on the Human Gene Therapy website.

About the Publisher

Mary Ann Liebert, Inc., publishers is known for establishing authoritative peer-reviewed journals in many promising areas of science and biomedical research. 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 more than 100 journals, books, and newsmagazines is available on the Mary Ann Liebert, Inc., publishers website.