DNA Insulator Enables Gene Expression, Generates Licenses and Royalties

DNA

Genes have control regions, called insulator elements, that dictate when, where, what, and how the gene will be expressed.

To leverage this espression, Drs. Jay Chung and Gary Felsenfeld of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) focused on the chemistry of interactions between DNA and regulatory proteins, particularly on the relationship between chromatin structure and gene expression.

In 1996 they isolated, identified and characterized a DNA sequence residing in chromatin from the chicken globin gene family, providing the first pure, functional, insulator element in mammalian cells.

Drs. Chung and Felsenfeld further demonstrated that the insulator molecule actively shields the expression of a gene from the regulatory effects of host chromatin while not disturbing the expression of the intended gene.

Their technology was patented in 1997 and has been used broadly by both academic and industry research scientists.

The seminal publication by Chung, Whitely and Felsenfeld, “A 5’ element of the chicken beta-globin domain serves as an insulator in human erythroid cells and protects against position effect in Drosophila,” has been cited by authors in scientific journals as well as patents more than 575 times. The insulator element has significantly advanced the way in which genetic research is conducted.

Fifteen years later, the DNA insulator element has been openly and widely shared with academic institutions for basic research under more than 265 material transfer agreements.

The applications for this technology are wide-ranging, perhaps limited only by the identity of the gene that may correlate to the condition of interest.

Academic scientists have used the insulator element for research in developmental biology to produce transgenic animals, as well as preclinical research into a variety of genetic diseases.

The NIH Office of Technology Transfer (OTT) has licensed this patented invention to for-profit companies in over 30 royalty-bearing licenses.

One such license is enabling a company to produce and extract human therapeutic proteins from the milk of transgenic animals by coupling the milk protein promoter to the gene of a desired protein.

The protein, which would otherwise be difficult to express or costprohibitive to manufacture utilizing traditional recombinant DNA technologies, is progressing to market.

NIDDK and the OTT have also arranged licenses to enable a company to market the insulator element as a research tool. Depending on the protein of interest, several different species may be used to produce protein in milk ranging from mice to rabbits, goats, and cows.

Goats have become perhaps the most popular as the tradeoffs in animal size, growth rate, and milk production are well-balanced.

Their milk provides the desired protein at 2-10 grams/liter. This work will undoubtedly pave the way for treatment of diseases that have no other protocols.

The royalty income resulting from the licenses has exceeded $900,000. Following NIH practice, these funds have been reinvested in the NIDDK intramural research program to further the NIH mission.

Dr. Felsenfeld continues to be interested in the function of insulator elements and the identification of factors that stabilize long-range interactions in the nucleus.