Nuclear reprogramming using IWSI and related chromatin remodeling ATPases

Patent Number: 7053264

This patent is useful for parties seeking to perform cloning or generate stem cells through cloning. During nuclear transfer mediated cloning, one of the difficulties is that the donor nucleus has DNA packed tightly into chromatin. During usual nuclear transfer it is the role of the recipient oocyte to unravel the DNA and to perform the necessary "cleaning of the slate" so that the nucleus is reprogrammed into its original, undifferentiated state and becomes totipotent. This patent teachs the use of existing chromatin remodeling proteins for making the job of the recipient oocyte easier. Specifically, the patent has 2 independent claims. The first covers a method of cloning, the other covers a method of performing nuclear transfer. Both claims cover the use of the remodelling proteins ISWI, SWI/SNF and Mi-2/CHD for "opening up" the chromatin. The author of the patent, now deceased, was an expert in nuclear remodelling. In one of his papers he states that as cells differentiate, there is "an assembly of specialized forms of repressive chromatin including linker histones, Polycomb group proteins and methyl-CpG-binding proteins" that makes them more difficult to be "reprogrammed" by nuclear transfer (Kikyo N et al. Reprogramming nuclei: insights from cloning, nuclear transfer and heterokaryons.J Cell Sci. 2000 Jan;113 ( Pt 1):11-20). This patent teaches one of the ways of "clearing out" these "specialized forms of repressive chromatin".

View this patent on the USPTO website.