To produce gene products at high levels of expression in a stable environment, typically a method for insertion of the gene into the host genome is used. Though this method can produce high expression clonal populations, the true parameters governing which cell clones are highly expressive is not known. We suggest that the epigenetic state around the insertion sites, both pre- and post-insertion, can play a critical role. We propose to characterize the epigenetic state, especially around insertion locations, and to evaluate epigenomic changes across cell lines and tissue.
How the Project May be Transformative and/or Benefit Society
Understanding how the epigenome affects insertion sites of DNA into the genome, and the subsequent expression of these inserted genes, could lead to more stable and productive clones. This will result in more productive cell lines, better characterization, and faster development times. With a greater understanding of the mechanisms involved in epigenetic regulation, we will enable lower cost of production and suggest methods to maintain high expression over time.
Site: Johns Hopkins University
Project Leaders: Winston Timp, Mike Betenbaugh