Arun Srivastava, PhD

Dr. Arun Srivastava is Professor in 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, in Gainesville, Florida, USA.

He has worked with AAV and AAV vectors for more than 44 years.

He received his PhD degree from the Indian Institute of Science in Bangalore, India. After completing his postdoctoral training at the Memorial Sloan-Kettering Cancer Center in New York, he worked as a Research Associate in the laboratory of Dr. Kenneth I. Berns at the University of Florida. For nearly two decades, he was on the faculty at Indiana University School of Medicine in Indianapolis, where he rose to the rank of Professor.

He was recruited back to the University of Florida in 2004 as George H. Kitzman Professor of Genetics and the Founding Chief of the Division of Cellular and Molecular Therapy. In the past over four decades, he has mentored 52 Postdoctoral and Clinical Fellows. Four students have graduated with MS degrees, and 12 students have received their PhD degrees from his laboratory.

He has received uninterrupted research funding for 42 years from the National Institutes of Health (NIH), and his current research is supported by grants from the NIH and the Children’s Miracle Network. He has also been awarded 21 US Patents with 22 additional US patent applications that have been filed on his research on AAV and their potential use as vectors in human gene therapy.

He currently serves on an NIH Study Section as well as on the Editorial Boards of Molecular Therapy, Human Gene Therapy, Journal of Virology, Journal of Gene Regulation, International Journal of Molecular Sciences, and Frontiers in Immunology, and Journal of Integrative Medicine. He also serves as Executive Editor of Journal of Genetic Syndromes & Gene Therapy, and Associate Editor of Vaccines & Molecular Therapeutics.

He has published 222 peer-reviewed research articles, book chapters, reviews, and miscellaneous articles, and 261 abstracts.

He was the founding scientist of the very first AAV gene therapy company, Avigen, which was launched in 1992. He was also a co-founder of a second AAV gene therapy company, Lacerta Therapeutics, which was launched in 2017. In 2023, he founded a third AAV gene therapy company, sAAVient Therapeutics.

His laboratory has developed the next generation (“NextGen”) AAV vectors in which the viral capsid has been modified to achieve high-efficiency transduction at significantly reduced vector doses. His laboratory has also modified the AAV genome to develop the generation X (“GenX”) AAV vectors with which increased transgene expression can be achieved. The NextGen AAV vectors have been used by other investigators in a Phase I/II Clinical Trial for Leber’s Hereditary Optic Neuropathy (LHON). The NextGen and the GenX vectors have been combined in his laboratory to develop the optimized (“OptX”) AAV serotype vectors that are more efficient at further reduced doses. Some of these AAV vectors have been licensed to various gene therapy companies.

Recently, his laboratory has developed generation Y (”GenY”) and “OptY” AAV vectors that are transcriptionally more efficient. More recently, his laboratory has also developed generation Z (”GenZ”), generation ZY (“GenZY”) and generation ZZ (”GenZZ”) AAV vectors that overcome the major rate-limiting step of viral second-strand DNA synthesis, and lead to robust transgene expression from single-stranded AAV serotype vectors.

His laboratory has also reported the development of AAV vectors that are capable of dampening the host humoral immune response as well. Efforts are currently to develop the ultimate (“Ult”) AAV vectors that may prove to be more efficient, less immunogenic, and capable of repeat-dosing.

His laboratory has also identified the remarkable tropism of two AAV vectors for primary human cells: AAV3 for liver, and AAV6 for hematopoietic stem cells. The current emphasis of his research is on gene therapy of genetic diseases such as hemophilia and muscular dystrophies; gene therapy of malignant disorders such as hepatoblastoma and hepatocellular carcinoma; and gene therapy and “nuclease-free” genome editing for β-thalassemia and sickle cell disease.

Dr. Srivastava’s research has been focused on the following two parvoviruses, the non-pathogenic adeno-associated virus (AAV), and a common human pathogen, the parvovirus B19, and the development of recombinant parvovirus vectors in human gene therapy. His laboratory has made seminal contributions to the field of parvoviruses, which include: identification of cellular co-receptors for AAV2 and AAV3 as well as parvovirus B19; elucidation of various steps involved in parvovirus trafficking in the cell and nuclear transport; identification of cellular proteins involved in the regulation of AAV DNA replication and encapsidation; development of recombinant AAV and parvovirus B19 vectors; and transgenic and knockout mouse models to study parvovirus-induced pathogenicity, and the use of parvovirus vectors for gene transfer and gene therapy.

His laboratory has developed the next generation (“NextGen”) AAV vectors in which the viral capsid has been modified to achieve high-efficiency transduction at significantly reduced vector doses. His laboratory has also modified the AAV genome to develop generation X (“GenX”) generation Y (“GenY”), and generation Z (“GenZ”) AAV vectors with which significantly increased transgene expression can be achieved. The NextGen AAV vectors have been used by other investigators in a Phase I Clinical Trial for Leber’s Hereditary Optic Neuropathy (LHON).

The NextGen capsids and the GenX and GenY genomes have been combined in Dr. Srivastava’s laboratory to develop the optimized [“OptX” and “OptY”] AAV serotype vectors, vectors that are more efficient at further reduced doses. Some of these AAV vectors have been licensed to various gene therapy companies.

His laboratory has also reported the development of AAV vectors that are capable of dampening the host humoral immune response as well. Efforts are currently to develop the ultimate (“Ult”) AAV vectors that may prove to be more efficient, less immunogenic, and capable of repeat-dosing.

Recently, his laboratory has developed generation Y (”GenY”) and “OptY” AAV vectors that are transcriptionally more efficient. More recently, his laboratory has also developed generation Z (”GenZ”), generation ZY (“GenZY”) and generation ZZ (”GenZZ”) AAV vectors that overcome the major rate-limiting step of viral second-strand DNA synthesis, and lead to robust transgene expression from single-stranded AAV serotype vectors.

His laboratory has also identified the remarkable tropism of two AAV vectors for primary human cells: AAV3 for liver, and AAV6 for hematopoietic stem cells. The current emphasis of his research is on gene therapy of genetic diseases such as hemophilia and muscular dystrophies; gene therapy of malignant disorders such as hepatoblastoma and hepatocellular carcinoma; and gene therapy and “nuclease-free” genome editing for β-thalassemia and sickle cell disease.

0000-0003-1168-8034

• Adeno-Associated Viral Gene Therapy
• Hematology
• Liver Disease