Mark Kay


Mark A. Kay MD, PhD, Dennis Farrey Family Professor in Pediatrics and Professor of Genetics, Stanford University School of Medicine


Research Description: Dr. Kay’s research over the last 23 years is related to gene therapy and non-coding RNA biology and he is an acknowledged leader in this field.  He has long been interested in the development of gene transfer vectors for gene therapy as well as manipulating non-coding RNAs for therapeutic purposes. His foundational studies have led to several multi-institutional human trials for gene therapy of conditions like hemophilia. A major interest has been in unraveling the mechanism of viral vector transduction in vivo. His work during the last 15 years has focused on two vector systems, mini-circles and recombinant AAVs (rAAV). Kay’s group has shown that DNA vectors consisting of a circularized eukaryotic expression cassette (lacking plasmid DNA backbone sequences) provide more persistent levels of transgene expression from quiescent tissues compared to the same plasmid vectors. Dr. Kay’s laboratory uncovered insights into how an Adenoviral vector expressing beta-cell transcription factors results in reprogramming of non-beta cells into functional beta-like cells in vivo. Dr. Kay has been an active member of the diabetes and islet biology community, with funded projects with Dr. Markus Grompe previously in the NIH/NIDDK Beta Cell Biology Consortium, and currently is a co-PI on a UO1 project of the Human Islet Resource Network in the Consortium for Targeting and Regeneration (CTAR). Their group is currently investigating mechanisms and methods to develop gene transfer vectors that when delivered by intravenous infusion target native islet cells, or re-program liver cells into functional human beta-cells.


Selected relevant publications (Stanford DRC members in BOLD):

  1. Nygaard S, Barzel A, Haft A, Major A, Finegold M, Kay MA, Grompe M. A universal system to select gene-modified hepatocytes in vivo. Sci Transl Med 8:342ra79, 2016.
  2. Valdmanis PN, Gu S, Chu K, Jin L, Zhang F, Munding EM, Zhang Y, Huang Y, Kutay H, Ghoshal K, Lisowski L, Kay MA. RNA interference-induced hepatotoxicity results from loss of the first synthesized isoform of microRNA-122 in mice. Nat Med 22:557-62, 2016.
  3. Kay, MA. Selecting the Best AAV Capsid for Human Studies. Mol Ther 23(12):1800-1, 2015.
  4. Human Sebastiano V, Zhen HH, Haddad B, Bashkirova E, Melo SP, Wang P, Leung TL, Siprashvili Z, Tichy A, Li J, Ameen M, Hawkins J, Lee S, Li L, Schwertschkow A, Bauer G, Lisowski L, Kay MA, Kim SK, Lane AT, Wernig M, Oro AE. COL7A1-corrected induced pluripotent stem cells for the treatment of recessive dystrophic epidermolysis bullosa. Sci Transl Med 6:264ra163, 2014.
  5. Phillips N, Kay MA. Characterization of vector-based delivery of neurogenin-3 in murine diabetes. Human Gene Therapy 25: 651-661, 2014.
  6. Wang Z, Lisowski L, Finegold MJ, Nakai H, Kay MA, Grompe M. AAV vectors containing rDNA homology display increased chromosomal integration and transgene persistence. Mol Ther 20:1902-11, 2012.