Joseph B. Lillegard, M.D., Ph.D., is developing cell-based and gene therapy cures for inborn errors of metabolism of the liver. Using viral and nonviral vectors, Dr. Lillegard is developing ex vivo, in vivo and in utero methods for delivery of advanced therapies for a variety of these severe metabolic diseases.
Dr. Lillegard is also advancing novel approaches for surgical fetal interventions, initially in the indication of spina bifida, where he is testing novel techniques and materials for repairing neural tube defects early in gestation to reduce the debilitating impact of these lesions.
- Developing models of metabolic liver disease. Dr. Lillegard and colleagues have developed genetically engineered models of hereditary tyrosinemia type 1 and phenylketonuria, which serve as experimental models for experimental gene therapy approaches intended for use in patients. They are also developing additional models to advance research for other diseases.
- In vivo gene therapy. Dr. Lillegard and colleagues are pioneering the use of viral and nonviral delivery systems for in vivo gene editing and gene delivery for multiple metabolic diseases of the liver. In addition, Dr. Lillegard's research group is pushing the field to consider direct therapeutic potential for lentivirus, which is considered an ex vivo vector.
- In utero gene transfer and gene delivery. Dr. Lillegard's laboratory is developing methods to safely and effectively target the in utero environment for gene therapy in an effort to cure patients before these diseases begin to manifest.
- Fetal surgical interventions. For diseases such as spina bifida, where there are improvements in outcomes for prenatal surgical intervention, Dr. Lillegard's laboratory is developing therapeutic approaches and materials for the earliest possible interventions, even without surgery.
Significance to patient care
Gene therapy is a rapidly evolving field with high potential to treat a variety of genetic disorders and provide cures for patients that currently face lifelong disease management regimens or highly invasive cures such as solid organ transplantation.
Dr. Lillegard's research expands the field's understanding of the potential for gene therapy in both viral and nonviral vectors, and target age for treatment, to include fetal interventions. This work aims to cure, or even prevent the onset of, diseases in patients carrying severe genetic deficiencies for which there are no available cures.