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August 12, 2020

Interview with Dr. Roland W. Herzog from IU School of Medicine

About Dr. Roland W Herzog

Dr. Roland W Herzog is a Professor of Pediatrics at the Riley Children’s Foundation. He is also a Director of the Gene and Cell Therapy Program at IU School of Medicine.

Some of Dr. Roland’s research interests include Gene therapy and immune tolerance for hemophilia – A disorder in which blood doesn’t clot normally. He is also the editor-in-chief for ASGCT’s field-leading journal (Molecular Therapy).

Today, we got the chance to interview Dr. Roland about his research on Gene Therapy. We asked a couple of questions to Dr. Roland, see below:

How did you come up with research on Liver Gene Therapy & what got you interested?

As a postdoctoral fellow, I was working on developing a gene therapy for the bleeding disorder hemophilia. The blood clotting factors that are missing in boys born with hemophilia are normally made in the liver, and methods were just emerging to effectively transfer genes to the liver in a way that the gene therapy could persist.

Hepatocytes, the main cells that make up the liver, are also great at producing large amounts of proteins and deliver them into the blood, so this seemed ideal. Moreover, we subsequently discovered that gene therapy to the liver can establish immune tolerance to the therapeutic proteins that are made as a result of gene transfer. This feature dramatically increases the chances that therapy will last rather than being rejected by the immune system.

Why is your research important? What are the possible real world applications?

My lab is now mostly focusing on the interactions between gene therapy and other therapies for genetic diseases and the immune system. For example, we typically use an engineered virus to deliver gene therapy. It is important to understand how the immune system responds to that. We need to make sure that the therapy is safe and that it lasts. We learned that, if done right, gene therapy can last for more than a decade, and likely even longer.

We are also developing other methods to teach the immune system to accept rather than reject therapeutics, for example by oral immunotherapy. Our main application is the treatment of hemophilia. In fact, the type of gene therapy that I have helped pioneer has shown much success in clinical trials and may become an approved drug over the next two years. Some of the methods that we developed to eliminate immune responses have now been successfully applied to patients. However, our work has implications for design of therapies for many other genetic diseases as well.

What question or challenge were you setting out to address when you started this work?

One of the early questions that we asked, once we knew how to deliver genes for therapeutic applications, was how the target organ may impact whether the immune system rejects the therapy or not. The liver stood out as an organ that is more likely to yield immune tolerance rather than immune rejection.

What do you want to achieve with your research?

I want to see a cure for patients with hemophilia become a reality. I also want to broaden and deepen our understanding of how gene and other therapies interact with the patient’s immune system and in the process make new discoveries about the immune system. Another very satisfying achievement is the training of scientists and helping to launch the careers of young scientists.

Tell me what you like to do when you aren’t working on research.

A vacation at the beach with some frozen drinks is always welcome. Otherwise, I like driving my classic sports car or simply enjoy a nice meal with a glass of wine with my wife or good friends.

What is your view on recent pandemic (COVID-19)?

Regarding coronavirus, I am not an expert on infectious disease or this class of viruses. Plus, data on immune responses in humans are only emerging and at times contradict each other, perhaps in part because of differences in assays and their reliability, or due to sample sizes and populations studied.

As someone who has been active in the gene therapy since the days when the American Society of Gene and Cell Therapy was founded, I am of course hopeful that a genetic vaccine will be effective against Coronavirus. DNA, viral vector-bsed, and mRNA vaccines have made major advances in recent year, so these technologies should be well positioned to offer a suitable vaccine.

How can our readers know more about your research?

Dr. Roland W Herzog lab website is: https://medicine.iu.edu/faculty-labs/herzog
My program’s website is: https://medicine.iu.edu/research-centers/pediatrics/research/gene-cell-therapy

 

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