Chromatin Insulator Protecting Expressed Genes of Interest for Human Gene Therapy or Other Mammalian Transgenic Systems

The technology provides the isolation of a functional DNA sequence comprising a chromatin insulating element from a vertebrate system and provides the first employment of the pure insulator element as a functional insulator in mammalian cells. The technology further relates to a method for insulating the expression of a gene from the activity of cis-acting regulatory sequences in eukaryotic chromatin.

This technology could be of major importance in providing a mechanism and a tool to restrict the action of cis-acting regulatory elements on genes whose activities or encoded products are needed or desired to be expressed in mammalian transgenic systems. This technology provides the first pure insulator element to function solely as an insulator element in human cells. Accordingly, this technology could have tremendous practical implications for transgenic technology and human gene therapies, either in vitro or in vivo.

The technology further provides a method and constructs for insulating the expression of a gene or genes in transgenic animals such that the transfected genes will be protected and stably expressed in the tissues of the transgenic animal or its offspring. For example, even if the DNA of the construct integrates into areas of silent chromatin in the genomic DNA of the host animal, the gene will continue to be expressed. The invention could provide a means of improving the stable integration and expression of any transgenic construct of interest, with efficiencies higher than are achieved presently. Use of this invention may represent a large potential savings for licensee's constructing transgenic cell lines or animals.