3357 – Enhancer Sequence for Improved Motor Neuron-Targeted Gene Therapy

Technology Summary This technology consists of a DNA construct for gene expression in spinal motor neurons that enables targeted gene therapy for motor neuron diseases. Technology Overview The homeobox gene Hb9 is expressed selectively by motor neurons in the developing CNS. Previous studies have identified a 9-kb 5’ fragment of the mouse Hb9 gene that is sufficient to direct gene expression to spinal motor neurons in vivo. However, the 9-kb Hb9 fragment is too long to be practical for gene therapy applications, where short regulatory elements are desired. Starting from the Hb9 gene fragment, the inventors identified a conserved 125 base pair regulatory element (enhancer) in the Hb9 promoter region that is sufficient to mediate expression of a gene of interest specifically in motor neurons. The expression system has been demonstrated in both in vitro and in vivo models, in which positioning a transgene downstream of the enhancer lead to selective expression in motor neurons. Thus, constructs employing the enhancer may be useful for gene therapy applications for motor neuron diseases. In addition, leveraging the enhancer to control a reporter gene can be used to isolate motor neurons from a mixed population of human brain and/or spinal cells, as well as to track the differentiation of human embryonic stem cells or induced pluripotent stem cells into motor neurons. Potential Applications Gene therapy for motor neuron diseases such as amyotrophic lateral sclerosis (ALS) or spinal muscular atrophy (SMA) Method to track or maximize the differentiation of stem cells into motor neurons Permits patient and disease-specific motor neurons to be identified and isolated for study Advantages Enables smaller constructs or targeting gene expression to motor neurons Limiting transgene expression to motor neurons may reduce off-target side effects Publications Nakano et al. “Identification of a conserved 125 base-pair Hb9 enhancer that specifies gene expression to spinal motor neurons.” Dev Biol. 2005. Roy et al. “Enhancer-specified GFP-based FACS purification of human spinal motor neurons from embryonic stem cells.” Exp Neurol. 2005. US Patent: 8,524,499. “Regulatory sequences that direct gene expression to spinal motor neurons and use thereof.” Granted Sep 3, 2013. Dan-Oscar Antson da429@cornell.edu 646-962-7042

Related Blog

Smart, interactive desk

Get ready to take your space management game to the next level with the University of Glasgow’s innovative project! By combining the

Mechanical Hamstring™

University of Delaware Technology Overview This device was created to allow athletes who suffer a hamstring strain to return to the field

Join Our Newsletter

                                                   Receive Innovation Updates, New Listing Highlights And More