Gene Therapy of Liver Cancer with AAV Vectors

Arun Srivastava, Ph.D.

Professor and Chief, Dept. of Pediatrics-Cellular and Molecular Therapy

Abstract: Two of the most common liver cancers include hepatoblastoma (HB) in children, and hepatocellular carcinoma (HCC) in adults. HB is the most frequent liver cancer in children in the United States. The median age at presentation is less than two years. Currently successful treatments are surgery and chemotherapy. While current treatments of HB are a vast improvement over those of 20 years ago, survivors suffer significant morbidity, and regardless of therapeutic improvements, 25% of affected children still die. Thus, a novel therapeutic approach for the treatment of HB is needed. HCC is the third most common cause of cancer-related deaths in adults worldwide, and more than 20,000 cases of HCC are diagnosed every year in the United States. The frequency of HCC and HCC-associated mortality have been increasing steadily. HCC is highly malignant, with an average survival rate of <1 year after the onset of symptoms. HCC is associated with liver cirrhosis in nearly all patients, and as a consequence, major surgical resections or chemotherapeutic interventions are not tolerated well. Thus, a novel therapeutic approach for the treatment of HCC is also needed. We are developing a novel gene therapy approach using a harmless virus, the adeno-associated virus (AAV), that causes no known disease in humans, to target both HB and HCC.

Dr. Arun Srivastava is the George H. Kitzman Professor of Genetics and Chief of the Division of Cellular & Molecular Therapy in the Departments of Pediatrics, and Molecular Genetics & Microbiology, and Powell Gene Therapy Center at the University of Florida College of Medicine. He has worked with AAV and AAV vectors for more than 43 years. He has received uninterrupted research funding for 38 years from the National Institutes of Health (NIH), and his current research is currently supported by grants from the NIH, Pfizer, Children’s Miracle Network, and the Kitzman Foundation. In addition to liver cancer, he is also pursuing gene therapy of hemophilia and muscular dystrophies, and genome editing for beta-thalassemia and sickle cell disease.

Core Standards

SC.912.N.1.3 Recognize that the strength or usefulness of a scientific claim is evaluated through scientific argumentation, which depends on critical and logical thinking, and the active consideration of alternative scientific explanations to explain the data presented.

SC.912.N.1.6 Describe how scientific inferences are drawn from scientific observations and provide examples from the content being studied.

SC.912.N.4.2 Weigh the merits of alternative strategies for solving a specific societal problem by comparing a number of different costs and benefits, such as human, economic, and environmental.

SC.912.L.14.2 Relate structure to function for the components of plant and animal cells. Explain the role of cell membranes as a highly selective barrier (passive and active transport).

SC.912.L.14.6 Explain the significance of genetic factors, environmental factors, and pathogenic agents to health from the perspectives of both individual and public health.

SC.912.L.16.8 Explain the relationship between mutation, cell cycle, and uncontrolled cell growth potentially resulting in cancer.

SC.912.L.16.7 Describe how viruses and bacteria transfer genetic material between cells and the role of this process in biotechnology.

SC.912.L.16.6 Discuss the mechanisms for regulation of gene expression in prokaryotes and eukaryotes at transcription and translation level.

SC.912.L.16.9 Explain how and why the genetic code is universal and is common to almost all organisms.

SC.912.L.16.10 Evaluate the impact of biotechnology on the individual, society and the environment, including medical and ethical issues.


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