Salk Institute

Technologies Available for Licensing

A Step Toward Safe Derivation of Clinically Relevant Human Induced Pluripotent Stem Cells

Inventors: Frederico Gonzalez and Juan Carlos Izpisua Belmonte
Potential Uses: Drug Discovery, Gene Expression, Research Tool, Stem Cells

A single plasmid construct that expresses four transcription factors from one polycistronic unit

Induced pluripotent stem (iPS) cells have generated keen interest due to their potential use in regenerative medicine. They have been obtained from various cell types of both mice and humans by exogenous delivery of different combinations of Oct4, Sox2, Klf4, c-Myc, Nanog, and Lin28. The delivery of these transcription factors has mostly entailed the use of integrating viral vectors (retroviruses or lentiviruses), carrying the risk of both insertional mutagenesis and oncogenesis due to misexpression of these exogenous factors. Therefore, obtaining iPS cells that do not carry integrated transgene sequences is an important prerequisite for their eventual therapeutic use.

We generated iPS lines in mice with no evidence of insertion of the reprogramming transgene into their genome by nucleofection of a single plasmid construct expressing four transcription factors (Oct4, Sox2, Klf4, and c-Myc) in one polycistronic unit. Using this strategy, we have obtained iPS clones with no evidence of transgene integration, thus avoiding the risk of reactivation leading to tumor formation. This approach represents a step forward for the safe derivation of clinical relevant human iPS cells.

Salk No: S09007
Patent Status: U.S. Patent Application filed March 2009
Publications: PNAS 106(22): 8918-22 (June 2009)
License Terms: Exclusive, Partially Exclusive, Nonexclusive license negotiable
Contact: Michelle Booden, Ph.D., Director of Licensing, 858.453.4100 x1612, mbooden@salk.edu

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