A Polycistronic Vector for Human iPS Cell Production

UAB Research Foundation
posted on 12/19/2011

Since 2006, many laboratories have reported successes in deriving induced pluripotent stem cells (iPS) from somatic cells. However, in most of these cases, the methods described were unable to avoid a stable integration of the reprogramming vector that could lead to potential activation or inactivation of endogenous genes. Researchers at The University of Alabama at Birmingham (UAB) have created a reprogramming lentiviral vector that can transduce adult dermal fibroblasts into iPS cell and later be removed.

Suggested Uses

Stem Cell Production

Advantages

Allows for reprogramming of adult dermal fibroblasts which are readily accessible by simple skin biopsies

Provides a reliable method of reprogramming somatic cells utilizing a single, self-inactivating, polycistronic lentiviral vector

Reprogramming sequence can easily be deleted from the iPS cell genome preventing unwanted inactivation or activation of endogenous genes

Provides the foundation for correcting hereditary disorders by reprogramming the generated iPS cells with the corrected gene

Innovation Details

Detailed Description

UAB researchers have created a single, polycistronic lentiviral vector encoding the reprogramming vectors Oct4, Sox2, and Klf4 with porcine teschovirus-1 2A sequence inserted between these factors. This polycistron was cloned downstream of an elongation factor 1α promoter in a self-inactivating lentiviral vector containing a loxP site. Using this vector, adult skin fibroblasts can be transduced into iPS cells capable of forming tissue derived from all three germ layer cell types. Expression of Cre recombinase in these iPS cells resulted in the deletion of the lentiviral vector with the exception of a small remnant piece that did not interrupt coding sequence or regulatory elements. Results of in vitro and in vivo studies show that this vector can safely and effectively reprogram adult skin fibroblasts into iPS cells to correct a hereditary disorder by gene replacement therapy.

File Number: U2008-0081

Web site: http://www.uab.edu/uabrf

Disease: Blood and Lymphatic System

Other Information:

MANAGING LICENSING ASSOCIATE

DEBORAH J. BIDANSET, PH.D., MBA

debbie@uab.edu (205) 975-6851

IP PROTECTION

U.S. Patent Application Serial No. 12/640,767, PCT filed December 17, 2009.

PRINCIPAL INVESTIGATOR

Tim Townes, Ph.D., Department of Biochemistry and Molecular Genetics, UAB.

IP Protection