Derivation of vector-free induced pluripotent stem (iPS) cells using site-specific DNA recombination

Referenznummer TO 01-00781

Challenge 
IPS cells have been regarded to be one of the top ten technologies in life science in 2008. The  market for stem cell applications is continuously growing. Products were virtually non-existent just five years ago but are projected at $2.7 billion in sales in 2012 with a projected market growth to $5 bil-lion in 2014.
IPS cells can be established from e.g. skin fibroblast by "reprogramming". These cells have the ability to self-renew and re-differentiate into a wide variety of cell types, comparable to embryonic stem (ES) cells but without the controversial ethical issues. The technology can be applied for research purposes, in drug screening, regenerative medicine, cell therapy, or gene therapy. Until now, there are no effective iPS-methods established that could be applied to humans for medical applications.

Technology

This invention addresses a novel method to generate iPS cells using site-specific DNA recombination for the cellular integration of reprogramming factors. The corresponding episomal vector system encompasses the reprogramming factors Sox2, Oct4, cMyc, Klf4 as well as Nanog or Lin28 flanked by loxP sites. After de-differentiation due to the expression of a set of reprogramming factors the vector copy can be removed by Cre-mediated recombination from established iPS cell lines. The advantage of targeted integration and excision of the reprogramming machinery should avoid side effects such as the development of cancerous cells and a potential disturbance of gene functions due to the reprogramming procedure, as known for the use of viral vector systems.

Commercial Opportunity

The technology is available for licensing or for a further collaborative development.

Developmental Status

An experimental proof of concept is in progress using mouse fibroblasts for the generation of iPS cells. Other research groups (Yu et al.) were already able to demonstrate that an episomal vector system can be used to reprogram human somatic cells into iPS cells.

Patent Situation

In March 2008 a priority claiming application was filed in Europe (EP08005378.8) followed by a PCT application (PCT/EP2009/001959) in 2009. 

Further Reading

Yu et al. (2009) Human induced pluripotent stem cells free of vector and transgene sequences, Science, 324:797. 

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Contact:

Sigrid Scheek, Ph.D.
Technology Manager
Ascenion GmbH

T: +49 (0)89 318814-34
F: +49 (0)89 318814-20
scheek@ascenion.de