Caroline Y. Kuo, M.D.

In addition to her clinical practice, Kuo has built a translational research program that revolves around the development of gene modification approaches for the treatment of rare immune deficiencies. Her research is focused on site-specific gene editing of blood stem cells for monogenic inborn errors of immunity using programmable nucleases such as TALENs and CRISPR/Cas9. Kuo is currently advancing a CRISPR/Cas9-based gene editing approach for X-linked Hyper IgM Syndrome to the pre-IND stage of development, as well as investigating methods to improve gene modification in stem cells without affecting their engraftment potential. 

Kuo is also working to develop a novel gene therapy to treat dedicator of cytokinesis 8 deficiency, or DOCK8 deficiency, a rare genetic disorder of the immune system characterized by frequent infections of the skin and respiratory system. Those with DOCK8 deficiency are currently treated with stem cell transplants from a matched donor, but these procedures carry the risk of graft-versus-host disease, a condition in which transplanted cells attack the recipient’s body. Kuo’s proposed approach genetically modifies a patient’s own blood stem cells to restore DOCK8 production, potentially shifting the paradigm through which patients with this condition are treated.

Kuo oversees additional projects at earlier stages of pre-clinical development investigating gene modification for other rare primary immune deficiencies and serves as principal investigator or co-investigator for clinical trials of lentiviral vector gene therapies for several inborn errors of immunity including X-linked chronic granulomatous disease and leukocyte adhesion deficiency type I.