Given all the developments in molecular genetics, the isolation and cloning of genes is now a relatively common procedure. Research now centers on somatic gene therapy, referring to the techniques used to insert a functioning gene into the somatic (non-reproductive) cells of a patient to correct an inborn genetic error or to provide a new function to the cell. Having individual genes available opens the way for gene therapy to take place. And yet, after an initial period of about six years of preclinical work and another thirteen years involving clinical trials, effective gene delivery still remains one of the central challenges in the field.
The Gene Therapy Program of the University of Pennsylvania comprises basic scientific research and core lab research services. Our focus is on developing effective gene vectors derived from recombinant viruses. Much of our current effort is in the development of new adeno-associated virus (AAV) vectors, although some of our research involves both adenoviruses and lentiviruses. Several basic science core laboratories work together to support the development of new vectors.
Learn more information about the Gene Therapy Program
Genetic counseling research
Active research projects include publishing case reports and series, and research about the provision of genetic counseling services. Genetic Counselors frequently submit abstracts to national meetings, such as the National Society of Genetic Counselors Annual Conference and the American College of Medical Genetics Annual Conference. Opportunities are available for students who are interested in working on thesis projects.
Genome editing program
The Genome Editing lab, led by Dr. Tobias Raabe, is focused on:
- The functional study of cardiovascular and liver disease associated gene mutations
- The development of regenerative medicine and gene therapy
- Establishing a robust method for the genetic manipulation of adult ductal liver stem cells
Our research is interested in isolating and characterizing adult ductal liver stem cells. We use special culture conditions that allow derivation of these resident ductal stem cells from adult mouse and human liver without artificial immortalization. These conditions allow for their continuous 3D culture for more than one year with a 10 fold higher genetic stability compared to iPSC cells.
In addition, the Genome Editing Program has several collaborations on campus, including research into cardiovascular disease, Alzheimer’s disease, and schizophrenia.
IRAD
The University of Pennsylvania is one of 19 sites around the world participating in IRAD — the International Registry of Acute Aortic Dissection. This project, active for more than a decade, enrolls people who are unfortunate to have suffered a sudden tear in the wall of their aorta. Dozens of important research papers have been published based on data accumulated by IRAD.
The principal investigators of the Penn site are Reed Pyeritz, MD, PhD, professor of medicine and genetics, and Joseph Bavaria, MD, professor of surgery. For more information, please contact Lisa Walsh at Lisa.Walsh@uphs.upenn.edu.
Orphan disease center
The ODC works to develop transformative therapies using platform technologies that can be deployed across multiple rare diseases. The Center focuses on disorders with substantial unmet need independent of their incidence and strives to assure access to patients of all populations.
The focus of the Center lies in partnership and leveraging of resources:
- Uniting investigators and clinicians within Penn and multiple institutions who are committed to treating and curing orphan disorders/diseases.
- Creating resources at Penn to enable discovery and preclinical development of potential therapies, as well as the clinical translation of those efforts.
- Extending approaches developed in one disorder to multiple others, and developing new technologically advanced research services to support this research.
- Providing a facile means for both small biotech and large pharmaceutical companies to partner with academic researchers in orphan disease research and therapeutic development.
- Linking academicians to both public and private foundations that support biomedical research for orphan diseases.
For more information, please visit the ODC website.
Pharmacogenomics research projects
Please contact Sony Tuteja, PharmD, MS at sonyt@pennmedicine.upenn.edu if you are interested in collaborating on pharmacogenomics research projects.
Impact of pharmacogenetic variants in the University of Pennsylvania Health System
Principal Investigator: Sony Tuteja, PharmD, MS
The goal of this project is to identify actionable pharmacogenetics variants within the Penn Biobank and develop methods to identify drug-related outcomes in the electronic health record. Learn more about Dr. Sony Tuteja’s Precision Medicine Accelerator Fund Project.
Clinical implementation of CYP2C19 testing
Investigators: Sony Tuteja, PharmD, MS and Jay Giri, MD, MPH
The goals of this project are to establish CYP2C19 as a clinical test, initiate and create clinical decision support tools within the electronic health record, create a workflow for pharmacogenetic test billing and assess economic impact, and assess the need for provider and patient education. CYP2C19-Clopidogrel testing information.
Assessment of prospective CYP2C19 genotype guided dosing of anti-platelet therapy in percutaneous coronary intervention (the ADAPT study)
Investigators: Sony Tuteja, PharmD, MS and Jay Giri, MD, MPH
The purpose of this study is to determine the clinical impact of CYP2C19 genotyping following percutaneous coronary intervention (PCI). Clinical trials.gov registration: NCT02508116. Assessment of Prospective CYP2C19 Genotype Guided Dosing of Anti-Platelet Therapy in Percutaneous Coronary Intervention (ADAPT).
Translational genome editing program
The Translational Genome Editing lab, led by Dr. Tobias Raabe, Ph.D. is focused on:
- Establishing robust CRISPR-mediated methods for the genetic manipulation of human-induced pluripotent stem cells (hiPSC) and of the newly discovered human liver-derived ductal stem cells
- The functional study of cardiovascular and liver disease associated gene mutations using induced hepatocytes derived from human liver-derived ductal stem cells
- The use of human liver-derived ductal stem cells for liver regenerative medicine and liver gene therapy
We are especially interested in isolating and characterizing adult liver-derived ductal stem cells, which are bi-potent cells that can give rise to either bile ducts or to hepatocytes, depending on their ex vivo or in vivo environment. We use special culture conditions that allow derivation of these resident ductal stem cells from adult mouse and, importantly, human liver without artificial transgene-based immortalization. These culture conditions allow for continuous 3D culture of the ductal stem cells for more than one year with a 10-fold higher genetic stability compared to iPSC. The human liver derived ductal stem cells are physiologically and genetically virtually identical to their precursors in the parental liver tissue and thus may yield more patient-relevant data compared to other cell types that have been traditionally used for the study of liver genetics, metabolism and disease.
In addition, the Translational Genome Editing Program has several collaborations on campus, including research into cardiovascular disease, Alzheimer’s disease and schizophrenia.