Arun Srivastava, Ph.D., a professor in the UF Departments of Pediatrics and Molecular Genetics & Microbiology, has been named a 2024 Fellow of the American Association for the Advancement of Science (AAAS), a distinguished lifetime honor in the scientific community.
Srivastava, a member of the Powell Gene Therapy Center, UF Genetics Institute and UF Health Cancer Center, was recognized for his distinguished contributions over more than four decades to the field of gene therapy. His fundamental studies of adeno-associated virus (AAV) molecular biology and the development of next-generation and optimized AAV vectors have paved the way for new and more effective treatments for genetic diseases.
Srivastava has received uninterrupted research funding for 41 years from the National Institutes of Health, been awarded 21 U.S. patents, founded four startups and mentored 45 postdoctoral and clinical fellows. His laboratory has identified two AAV vectors that efficiently transduce primary human cells, and his current research focuses on gene therapy for genetic diseases such as hemophilia and muscular dystrophies, malignant disorders such as liver cancers, and “nuclease-free” genome editing for β-thalassemia and sickle cell disease.
“I’m very grateful for this honor and very fortunate,” Srivastava said. “I think about AAV constantly and I’m excited to come to work every day. I couldn’t be more grateful for the opportunities I have had, which have hopefully translated into something meaningful.”
AAAS is the world’s largest general scientific society and publisher of the Science family of journals. The honor, which includes alumni such as Thomas Edison and W.E.B. DuBois, is among the most distinctive in academia and recognizes extraordinary impact and achievement across disciplines. Srivastava is one of 14 UF faculty members elected 2024 Fellows.
“Dr. Srivastava’s contributions to the field of gene therapy have been enormous, including the development of vectors that are more efficient and less immunogenic,” said Rashmin Savani, M.B., Ch.B., professor, Nemours Eminent Scholar and chair of the Department of Pediatrics. “Despite these amazing achievements, he remains humble and kind, and his singular focus is on helping patients with genetic disorders.”
“His singular focus is on helping patients with genetic disorders.”
Gene therapy with AAV vectors uses a harmless, engineered virus to deliver a functioning copy of a defective gene. UF is known as the birthplace of AAV — the first recombinant AAV vector was created at UF — and it remains preeminent in the field. In 2023, UF was named the world’s top contributor to scientific knowledge and literature about AAV vectors.
Srivastava’s interest in AAV was sparked as a first-year graduate student when he read a paper in Nature proposing a model of how a single-stranded DNA replicates, prompting him to search for an existing organism with single-stranded DNA. That led him to the “godfather of AAV” who is credited with much of UF’s groundbreaking AAV research: the late Kenneth Berns, M.D., Ph.D.
Srivastava joined Berns’ lab as a research associate after his postdoctoral training at Memorial Sloan Kettering Cancer Center in New York. He later joined the faculty at Indiana University School of Medicine, where he made fundamental discoveries about AAV.
“We showed that AAV infection requires a receptor on cells, which opened up the whole field of vector biology,” said Srivastava, who was the founding scientist of the first AAV gene therapy company, Avigen, in 1992.
In 2004, Srivastava was recruited back to UF as the George H. Kitzman Professor of Genetics and the founding chief of the Division of Cellular and Molecular Therapy in the Department of Pediatrics. The division has been highly successful, maintaining $3 to $5 million in research funding per year.
In 2006, the “lightbulb went on” as Srivastava realized the need to make a vector distinct from the naturally occurring AAV so that the human immune system wouldn’t recognize it. These highly efficient “next-generation” vectors went on to be used successfully in a Phase I/II clinical trial for Leber hereditary optic neuropathy.
Since then, his lab has developed an array of next-generation and optimized vectors, some of which have been licensed to gene therapy companies. Twenty-two U.S. patent applications have been filed on Srivastava’s research on AAV and their potential use as vectors in human gene therapy.
More recently, Srivastava’s lab has identified two AAV vectors that will efficiently transduce primary cells: AAV3 for the liver and AAV6 for bone marrow stem cells. He anticipates launching a clinical trial to test AAV3 as a gene therapy for hemophilia B later this year.
“We hope that these next-generation vectors will be safer and more efficient at much lower doses,” Srivastava said.
Guided by Berns and his mentors, the late Nicholas Muzyczka, Ph.D., and Mavis Agbandje-McKenna, Ph.D. — all titans in the field — Srivastava maintains an abiding belief in the power of basic science to unlock clues to cure difficult genetic diseases.
“Anybody can make a vector, but if you understand the biology of AAV, it is truly amazing,” he said.
This pursuit propels him forward as he marks 45 years in research. His lab continues to refine the vector capsid as well as the genome for greater efficiency and safety for gene therapy of human diseases.
“AAV continues to provide new avenues to pursue, and we keep coming up with good ideas to answer some of the problems in the field,” Srivastava said.
In the early days of AAV research, some researchers disparaged it by redefining the acronym as “almost a virus.” Berns, Srivastava’s mentor, later gave it his own twist: “an awesome vector.”
Now, Srivastava wants to put forth his own: “an amazing virus.”
