NU 2007-020

Inventors

David Dean*

R. Christopher Geiger

Short Description

Novel method for increasing gene transfer by inhibition of histone deacetylase enzymes

Abstract

Northwestern researchers have developed a method for improving gene expression of genes delivered for therapeutic applications. One of the main obstacles to establishing effective non-viral gene therapies is inefficient delivery of genes into the nucleus where they can be expressed. While various methods have been developed to accomplish this, none overcome the intrinsic cellular protein (HDAC6) that actively impedes transport of genes to the nucleus by destabilizing the microtubules. Prof. Dean and colleagues developed a method for increasing gene expression that centers on inhibiting HDAC6, so that genes are more effectively transported into the nucleus. In laboratory tests, HDAC6 inhibition facilitated a 10- to 100-fold increase gene expression in lung cells as early as 2 hours post transfection. This technique should be applicable to any cells that endogenously express HDAC6. Importantly, histone deacetylase inhibitors are being investigated in clinical trials, so it is possible that HDAC6 inhibitor that is safe and effective for use in humans will be identified. This invention could be combined with current transfection technologies to enable more effective gene transfer for clinical and research purposes.

Applications

• Non-viral gene therapy for various diseases
• Research reagent

Advantages

• Simple to use
• High gene expression efficiency

Publications

Vaughan EE, Geiger RC, Miller AM, Loh-Marley PL, Suzuki T, Miyata N, Dean DA (2008) Microtubule Acetylation Through HDAC6 Inhibition Results in Increased Transfection Efficiency, Molecular Therapy. 16: 1841-1847.

IP Status

Issued US patent 8,334,272