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INVENTIONS FOR LICENSE

MCL 20164.0: Generation of iPS Cells by Direct Protein Delivery

Kwang-Soo Kim, Ph.D., et al.

Background and Description

The field of stem cell biology was revolutionized several years ago by the discovery that differentiated cells, such as adult somatic cells, could be induced to dedifferentiate into a pluripotent state by forcing the expression of genes encoding the transcription factors Oct-3/4, SOX2, c-Myc, and Klf4 ("reprogramming factors") to reset the cell's genotype to that of a pluripotent state. The resulting cells, called induced pluripotent ("iPS") cells, are believed to be identical to natural pluripotent stem cells such as embryonic stem cells, with regard to the expression of certain stem cell genes and proteins, potency and differentiability, and other key characteristics. The originally-derived methods for reprogramming differentiated cells require the use of viral vectors to express the reprogramming factor genes, which can be undesirable because viral vectors are known to integrate into host cell genome, possibly causing harm to the cell and the organism. The present invention provides an alternative method of producing iPS cells that avoids such difficulties or disadvantages. In the improved method, purified reprogramming factor proteins are fused (e.g. chemically or through recombinant expression) with a cationic conjugate, such as a lysine-rich peptide, and added to cultures of the desired starting cell. The cationic portion of the hybrid molecule facilitates entry of the proteins into the cells, to allow the reprogramming factors to induce dedifferentiation of the cells and the creation of iPS cells.

Potential Commercial Uses

The invention affords a powerful new approach to creation of iPS cells without the need for viral vectors or other problematic ways of expressing the preprogramming proteins. The method can be used with any adult somatic cells, including cells from those afflicted with a disease of interest. The resulting iPS cells can be used to regenerate adult tissue of various cell types, to be used for research purposes or for development of therapeutic protocols for disease treatment

Publication and Patent Status

A PCT patent application claiming this invention has been filed. The research underlying the invention has been published as Kim et al., Cell Stem Cell. 2009 June 5; 4(6): 472476.

Licenses Available

McLean Hospital is offering licenses to this technology for the development of therapeutic or other products using this method.

For more information, please contact:

David J. Glass, Ph.D.
Senior Associate Director, Technology Transfer
McLean Hospital Research Administration
115 Mill Street
Belmont, MA 02478-9106
(617) 855-3825 - tel
(617) 855-3745 - fax
dglass@mclean.harvard.edu