James Wilson (scientist)

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James M. Wilson
Alma mater Albion College, University of Michigan
Known for Gene Therapy
Scientific career
Institutions Perelman School of Medicine
Doctoral advisor William N. Kelley

James M. Wilson is an American biomedical researcher who serves as the Director of the Gene Therapy Program, Rose H. Weiss Professor and Director of the Orphan Disease Center, and Professor of Medicine and Pediatrics at the Perelman School of Medicine at the University of Pennsylvania. [1] Previously, he held the John Herr Musser endowed professorship at the Perelman School of Medicine. [2]

Contents

Education and Research

Wilson graduated from Albion College (B.A., Chemistry) and the University of Michigan (MD, PhD). [3]  He completed residency training in Internal Medicine at the Massachusetts General Hospital followed by a postdoctoral fellowship at the Whitehead Institute. [4]

Wilson’s research involves the development of viral-based gene therapies for genetic diseases. A major research focus is the generation of novel vectors for improved transduction efficiencies and regulated expression, as well as the elucidation of host immune responses to viral vectors. [5] His work emphasizes the creation of vectors for in vivo gene therapy concentrating on adeno-associated viruses. This work began with the discovery in his laboratory of a new family of primate AAVs; over 120 new AAV capsids were rescued as latent genomes from primate tissues and studied for their biology and potential as vectors. [6] [7] This has led to an enhanced understanding of vector host interactions and a new generation of vectors with substantially improved performance profiles beyond that provided from the original 6 AAV isolates. More recently, Wilson’s laboratory has used AAV to accomplish successful in vivo genome editing. [8] [9] As of 2018, his laboratory’s translational research portfolio included more than 30 orphan disease programs. [10]

The adeno-associated viruses serotypes discovered in Wilson's lab were used in several clinically approved gene therapies including onasemnogene abeparvovec which uses AAV9. Wilson is the founder of several gene therapy companies including Genovo, Regenxbio, Passage Bio, and Scout Bio. [11]

Jesse Gelsinger

In 1999, Wilson led a clinical trial at the Institute for Human Gene Therapy using an adenoviral vector that resulted in the death of Jesse Gelsinger. As a result, the government banned him from working on FDA-regulated human clinical trials for five years and shut down the institute, which led to a shift in his research focus towards a study of adeno-associated viruses (AAV). [12] [11]

Related Research Articles

<span class="mw-page-title-main">Gene therapy</span> Medical field

Gene therapy is a medical technology that aims to produce a therapeutic effect through the manipulation of gene expression or through altering the biological properties of living cells.

<span class="mw-page-title-main">Adeno-associated virus</span> Species of virus

Adeno-associated viruses (AAV) are small viruses that infect humans and some other primate species. They belong to the genus Dependoparvovirus, which in turn belongs to the family Parvoviridae. They are small replication-defective, nonenveloped viruses and have linear single-stranded DNA (ssDNA) genome of approximately 4.8 kilobases (kb).

<span class="mw-page-title-main">Viral vector</span> Biotechnology to deliver genetic material into a cell

Viral vectors are modified viruses designed to deliver genetic material into cells. This process can be performed inside a living organism or in cell culture. They have widespread applications in basic research, therapies, and vaccines.

Gene therapy using lentiviral vectors was being explored in early stage trials as of 2009.

Retinal gene therapy holds a promise in treating different forms of non-inherited and inherited blindness.

<span class="mw-page-title-main">Alipogene tiparvovec</span>

Alipogene tiparvovec, sold under the brand name Glybera, is a gene therapy treatment designed to reverse lipoprotein lipase deficiency (LPLD), a rare recessive disorder, due to mutations in LPL, which can cause severe pancreatitis. It was recommended for approval by the European Medicines Agency in July 2012, and approved by the European Commission in November of the same year. It was the first marketing authorisation for a gene therapy treatment in either the European Union or the United States.

Self-complementary adeno-associated virus (scAAV) is a viral vector engineered from the naturally occurring adeno-associated virus (AAV) to be used as a tool for gene therapy. Use of recombinant AAV (rAAV) has been successful in clinical trials addressing a variety of diseases. This lab-made progeny of rAAV is termed "self-complementary" because the coding region has been designed to form an intra-molecular double-stranded DNA template. A rate-limiting step for the standard AAV genome involves the second-strand synthesis since the typical AAV genome is a single-stranded DNA template. However, this is not the case for scAAV genomes. Upon infection, rather than waiting for cell mediated synthesis of the second strand, the two complementary halves of scAAV will associate to form one double stranded DNA (dsDNA) unit that is ready for immediate replication and transcription. The caveat of this construct is that instead of the full coding capacity found in rAAV (4.7–6kb) scAAV can only hold about half of that amount (≈2.4kb).

<span class="mw-page-title-main">Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations</span> Medical condition

Retinal vasculopathy with cerebral leukocencephalopathyand systemic manifestations is an inherited condition resulting from a frameshift mutation in the C-terminal region of the TREX1 gene. This disease affects small blood vessels, leading to damage of multiple organs including but not limited to the retina and the white matter of the central nervous system. Patients with RVCL develop vision loss, brain lesions, strokes, brain atrophy, and dementia. Patients with RVCL also exhibit other organ involvement, including kidney, liver, gastrointestinal tract, thyroid, and bone disease. Symptoms of RVCL commonly begin between ages 35 and 55, although sometimes disease onset occurs earlier or later. The overall prognosis is poor, and death can sometimes occur within 5 or 10 years of the first symptoms appearing, although some patients live more than 20 years after initial symptoms. Clinical trials are underway, as are efforts to develop personalized medicines for patients with RVCL.

Saswati Chatterjee is a virologist working as a professor at the Los Angeles City of Hope National Medical Center in the research department. Some of the viral areas she researches are: stem cells, gene therapy, genome editing, and parvovirus. Her main and current area of research is using Adeno-Associated Virus Vectors (AAV-Vectors). Additionally, she has had a role in many publications.

<span class="mw-page-title-main">Mark Batshaw</span> American geneticist

Mark Levitt Batshaw is a Canadian-born physician, medical researcher and academic administrator. He was a professor in the department of pediatrics and an associate dean at the George Washington University School of Medicine & Health Sciences and was the physician-in-chief and chief academic officer at Children’s National Hospital in Washington, D.C. He is known for his research into urea cycle disorders and gene therapy, and is the author of the classic textbook "Children with Disabilities".

Katherine A. High is an American doctor-scientist who is an emeritus professor at the Perelman School of Medicine at the University of Pennsylvania. She was the co-founder, president, and chief scientific officer of Spark Therapeutics and currently serves as President of Therapeutics at AskBio. Her career has focused on pioneering work in the area of gene therapy, with many accomplishments in basic, translational, and clinical investigation in gene therapy.

Adeno-associated virus (AAV) has been researched as a viral vector in gene therapy for cancer treatment as an oncolytic virus. Currently there are not any FDA approved AAV cancer treatments, as the first FDA approved AAV treatment was approved December 2017. However, there are many Oncolytic AAV applications that are in development and have been researched.

Richard Jude Samulski is an American scientist, inventor, and academic recognized for his pioneering work in gene therapy and adeno-associated virus vectors (AAV) in the fields of molecular virology and pharmacology.

Jean Bennett is the F. M. Kirby Professor of Ophthalmology in the Perelman School of Medicine at the University of Pennsylvania. Her research focuses on gene therapy for retinal diseases. Her laboratory developed the first FDA approved gene therapy for use in humans, which treats a rare form of blindness. She was elected a member of the National Academy of Sciences in 2022.

Sara R. Cherry is an American microbiologist who is John W. Eckman Professor of Medical Science and Professor of Microbiology in Biochemistry and Biophysics at the Perelman School of Medicine at the University of Pennsylvania. Her research involves genetic and mechanistic studies of virus–host interactions. During the COVID-19 pandemic, Cherry looked to identify novel therapeutic strategies.

Mavis Agbandje-McKenna was a Nigerian-born British medical biophysicist, structural virologist, and a professor of structural biology, as well as the director of the Center for Structural Biology at the University of Florida in Gainesville, Florida. Agbandje-McKenna studied parvovirus structures using X-ray crystallography and cryogenic electron microscopy and did much of the initial work to elucidate the basic structure and function of adeno-associated viruses (AAVs). Her viral characterization and elucidation of antibody binding sites on AAV capsids has led to the development of viral capsid development and gene therapy approaches that evade immune detection and can be used to treat human diseases such as muscular dystrophies. Agbandje-McKenna was recognized with the 2020 American Society of Gene and Cell Therapy Outstanding Achievement Award for her contributions to the field. She died in 2021 from amyotrophic lateral sclerosis.

Beverly L. Davidson is an American geneticist. She is the director of the Raymond G. Perelman Center for Cellular and Molecular Therapeutics at Children's Hospital of Philadelphia. In this role, she investigates gene therapy for neurodegenerative diseases, specifically Huntington's.

<span class="mw-page-title-main">Erika Holzbaur</span> American biologist

Erika L F. Holzbaur is an American biologist who is the William Maul Measey Professor of Physiology at University of Pennsylvania Perelman School of Medicine. Her research considers the dynamics of organelle motility along cytoskeleton of cells. She is particularly interested in the molecular mechanisms that underpin neurodegenerative diseases.

Avalotcagene ontaparvovec (DTX301) is "a non-replicating, recombinant self-complimentary adeno-associated virus vector serotype 8 (scAAV8)-encoding human ornithine transcarbamylase". It is developed by Dimension Therapeutics for ornithine transcarbamylase (OTC) deficiency.

References

  1. ↑ "University of Pennsylvania Gene Therapy Program | Our Team". gtp.med.upenn.edu. Retrieved 2018-09-28.
  2. ↑ "John Herr Musser Professorship of Research Medicine | Endowed Professorships | Perelman School of Medicine at the University of Pennsylvania". www.med.upenn.edu.
  3. ↑ "James M. Wilson | Faculty | About Us | Perelman School of Medicine | Perelman School of Medicine at the University of Pennsylvania". www.med.upenn.edu. Retrieved 2018-09-28.
  4. ↑ "James M. Wilson - Faculty Biosketch". www.med.upenn.edu. Retrieved 2018-09-28.
  5. ↑ "University of Pennsylvania Gene Therapy Program | Home". gtp.med.upenn.edu. Retrieved 2018-09-28.
  6. ↑ Gao, Guang-Ping; Alvira, Mauricio R.; Wang, Lili; Calcedo, Roberto; Johnston, Julie; Wilson, James M. (2002-09-03). "Novel adeno-associated viruses from rhesus monkeys as vectors for human gene therapy". Proceedings of the National Academy of Sciences of the United States of America. 99 (18): 11854–11859. Bibcode:2002PNAS...9911854G. doi: 10.1073/pnas.182412299 . ISSN   0027-8424. PMC   129358 . PMID   12192090.
  7. ↑ Gao, Guangping; Vandenberghe, Luk H.; Alvira, Mauricio R.; Lu, You; Calcedo, Roberto; Zhou, Xiangyang; Wilson, James M. (June 2004). "Clades of Adeno-associated viruses are widely disseminated in human tissues". Journal of Virology. 78 (12): 6381–6388. doi:10.1128/JVI.78.12.6381-6388.2004. ISSN   0022-538X. PMC   416542 . PMID   15163731.
  8. ↑ Yang, Yang; Wang, Lili; Bell, Peter; McMenamin, Deirdre; He, Zhenning; White, John; Yu, Hongwei; Xu, Chenyu; Morizono, Hiroki (March 2016). "A dual AAV system enables the Cas9-mediated correction of a metabolic liver disease in newborn mice". Nature Biotechnology. 34 (3): 334–338. doi:10.1038/nbt.3469. ISSN   1546-1696. PMC   4786489 . PMID   26829317.
  9. ↑ Wang, Lili; Smith, Jeff; Breton, Camilo; Clark, Peter; Zhang, Jia; Ying, Lei; Che, Yan; Lape, Janel; Bell, Peter (September 2018). "Meganuclease targeting of PCSK9 in macaque liver leads to stable reduction in serum cholesterol". Nature Biotechnology. 36 (8): 717–725. doi:10.1038/nbt.4182. ISSN   1546-1696. PMID   29985478. S2CID   51600299.
  10. ↑ "University of Pennsylvania Gene Therapy Program | Translational Research Lab". gtp.med.upenn.edu. Retrieved 2018-09-28.
  11. 1 2 Cross, Ryan (12 September 2019). "The redemption of James Wilson, gene therapy pioneer". Chemical & Engineering News. No. 36.
  12. ↑ Zimmer, Carl (August 13, 2013). "Gene Therapy Emerges From Disgrace to Be the Next Big Thing, Again". Wired– via www.wired.com.
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