David T. Curiel | |
---|---|
Born | 1956 (age 66–67) |
Academic background | |
Education | BSc, Chemistry, 1978, West Georgia College MD, 1982, Emory University School of Medicine PhD, Virology, 2002, University of Groningen |
Thesis | Genetic capsid modification for adenovirus retargeting (2002) |
Academic work | |
Institutions | Washington University in St. Louis University of Alabama at Birmingham University of North Carolina at Chapel Hill |
David Terry Curiel (born 1956) is an American cancer biologist. He is a professor of Radiation Oncology at Washington University School of Medicine and Director of the Biologic Therapeutics Center. In 1995,Curiel led a research team who were the first to develop a vaccine based on messenger RNA. Although they published proof of concept,he could not continue testing due to a lack of funding. In 2021,Curiel developed a vaccine that targets the SARS-CoV-2 virus through the nose.
Curiel was born in 1956 [1] in the Douglasville,Georgia area. [2] His father,a general practitioner, [2] immigrated to the United States from the Dominican Republic. Curiel is of Jewish descent. [3] Following high school,Curiel remained in his home state for his Bachelor of Science degree at West Georgia College and medical degree at the Emory University School of Medicine. Upon receiving his medical degree,Curiel completed his internship and residency at Emory in 1985 and his fellowships in pulmonary medicine and biotechnology at the National Institutes of Health in 1990. [4] He enrolled at the University of Groningen in the Netherlands for his PhD. [5]
Following his fellowships,Curiel became an assistant professor of medicine at the University of North Carolina at Chapel Hill (UNC). [6] In this role,he began working on gene transfer techniques for the treatment of cystic fibrosis. In 1992,he began combining two different gene therapy approaches into a virus using Adenovirus. Healthy genes are transferred to defective cells on the outer coat of inactivated adenoviruses which in turn enter the cell nuclei where defective genes lie. [7] [8] His research efforts earned him the 1992 James W Woods Junior Faculty Award from UNC. [6] Following this,Curiel was appointed Director of the University of Alabama at Birmingham's (UAB) Gene Therapy Program in 1993. [2] While serving in this role,Curiel led a research team who were the first to develop a vaccine based on messenger RNA. Although they published proof of concept,he could not continue testing due to a lack of funding and public interest. [9] Curiel also served as the principal investigator (PI) of a team researching how to develop unique methods of delivering genes to specific targets. [10] His efforts in gene therapy earned him the funding to study a system to define tumor cell signatures. [11] In January 2000,Curiel was appointed Director of the Division of Human Gene Therapy at UAB's Heersink School of Medicine. [2]
As Director of the Division of Human Gene Therapy,Curiel oversaw a consortium of scientists who modified an adenovirus that reproduces inside tumor cells in order to eradicate them called Delta-24-RGD. [12] This was thought to be the first treatment for malignant glioma. While testing the Delta-24-RGD treatment with scientists at the MD Anderson Cancer Center,their research teams found that the treatment would completely eradicate brain tumors in mice,while leaving healthy brain tissue alone. [13] He also founded VectorLogics,Inc. in order to develop products to treat ovarian cancer. [14] In 2004,Curiel was a finalist for the Director position at the University of Arizona's Institute for Biomedical Science and Biotechnology. [5] However,he chose to remain at UAB until 2011 when he became Director of Washington University in St. Louis' (WUSTL) Biologic Therapeutics Center. [15] During his final years at UAB,Scientific American magazine deemed Curiel's 2003 co-authored paper on virotherapy as "one of 10 groundbreaking stories of the past 10 years." [16] [17]
Upon joining the faculty at WUSTL in 2011,Curiel was appointed a professor of radiation oncology with tenure. [18] He also merged his company VectorLogics,Inc. with DNAtrix,a biotechnology company developing targeted adenovirus-based oncolytic virus products for brain cancer. [14] In 2012,Curiel collaborated with scientist Mike Mathis from LSU to test the adenovirus on colon cancer in mice. [19] These experiments resulted in the discovery that the adenovirus could target tumor blood vessels in mice without affecting healthy tissues. [20] His use of viral vector technology to optimize the immune system's response to vaccines earned him one of the 2015 Bear Cub Challenge award from the Skandalaris Center for Interdisciplinary Innovation and Entrepreneurship. [21] Due to the 2015–16 Zika virus epidemic,Curiel and Precision Virologics commercialized an adenovirus vaccine to prevent the disease and others. [22] In 2019,he received funding from the National Center for Advancing Translational Sciences to support his research into discovering new therapeutics for genetic diseases. [23] This eventually developed into a new approach to facilitate the "CAR-T" immunotherapy that makes it cheaper and more patient-accessible. [24]
During the COVID-19 pandemic,Curiel harnessed gene therapy and viral vectors to develop therapeutics and vaccines to combat the novel coronavirus. [25] Early in the pandemic,Curiel and Michael S. Diamond re-engineered Adenovirus to carry the Sars-Covid2 spike gene in order to protect against infection and sterilize the upper airways. Their single-dose,nasal vaccine was proven successful in mice and nonhuman primates which led them to begin trials in India with Bharat Biotech. [26] [27] Curiel was later named a senior member of the National Academy of Inventors for his gene-therapy research. [28] In late January 2023,the nasal vaccine received approval from India's Ministry of Health and Family Welfare and Science and Technology Minister Jitendra Singh to be added to the primary 2-dose schedule. [29]
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.
Adenoviruses are medium-sized,nonenveloped viruses with an icosahedral nucleocapsid containing a double-stranded DNA genome. Their name derives from their initial isolation from human adenoids in 1953.
In the field of genetics,a suicide gene is a gene that will cause a cell to kill itself through the process of apoptosis. Activation of a suicide gene can cause death through a variety of pathways,but one important cellular "switch" to induce apoptosis is the p53 protein. Stimulation or introduction of suicide genes is a potential way of treating cancer or other proliferative diseases.
SV40 is an abbreviation for simian vacuolating virus 40 or simian virus 40,a polyomavirus that is found in both monkeys and humans. Like other polyomaviruses,SV40 is a DNA virus that sometimes causes tumors in animals,but most often persists as a latent infection. SV40 has been widely studied as a model eukaryotic virus,leading to many early discoveries in eukaryotic DNA replication and transcription.
A cancer vaccine is a vaccine that either treats existing cancer or prevents development of cancer. Vaccines that treat existing cancer are known as therapeutic cancer vaccines or tumor antigen vaccines. Some of the vaccines are "autologous",being prepared from samples taken from the patient,and are specific to that patient.
An oncolytic virus is a virus that preferentially infects and kills cancer cells. As the infected cancer cells are destroyed by oncolysis,they release new infectious virus particles or virions to help destroy the remaining tumour. Oncolytic viruses are thought not only to cause direct destruction of the tumour cells,but also to stimulate host anti-tumour immune system responses. Oncolytic viruses also have the ability to affect the tumor micro-environment in multiple ways.
Virotherapy is a treatment using biotechnology to convert viruses into therapeutic agents by reprogramming viruses to treat diseases. There are three main branches of virotherapy:anti-cancer oncolytic viruses,viral vectors for gene therapy and viral immunotherapy. These branches use three different types of treatment methods:gene overexpression,gene knockout,and suicide gene delivery. Gene overexpression adds genetic sequences that compensate for low to zero levels of needed gene expression. Gene knockout uses RNA methods to silence or reduce expression of disease-causing genes. Suicide gene delivery introduces genetic sequences that induce an apoptotic response in cells,usually to kill cancerous growths. In a slightly different context,virotherapy can also refer more broadly to the use of viruses to treat certain medical conditions by killing pathogens.
A short hairpin RNA or small hairpin RNA is an artificial RNA molecule with a tight hairpin turn that can be used to silence target gene expression via RNA interference (RNAi). Expression of shRNA in cells is typically accomplished by delivery of plasmids or through viral or bacterial vectors. shRNA is an advantageous mediator of RNAi in that it has a relatively low rate of degradation and turnover. However,it requires use of an expression vector,which has the potential to cause side effects in medicinal applications.
Viral vectors are tools commonly used by molecular biologists to deliver genetic material into cells. This process can be performed inside a living organism or in cell culture. Viruses have evolved specialized molecular mechanisms to efficiently transport their genomes inside the cells they infect. Delivery of genes or other genetic material by a vector is termed transduction and the infected cells are described as transduced. Molecular biologists first harnessed this machinery in the 1970s. Paul Berg used a modified SV40 virus containing DNA from the bacteriophage λto infect monkey kidney cell maintained in culture.
An adenovirus vaccine is a vaccine against adenovirus infection. According to American CDC,"There is currently no adenovirus vaccine available to the general public.
A genetically modified virus is a virus that has been altered or generated using biotechnology methods,and remains capable of infection. Genetic modification involves the directed insertion,deletion,artificial synthesis or change of nucleotide bases in viral genomes. Genetically modified viruses are mostly generated by the insertion of foreign genes intro viral genomes for the purposes of biomedical,agricultural,bio-control,or technological objectives. The terms genetically modified virus and genetically engineered virus are used synonymously.
Gene therapy utilizes the delivery of DNA into cells,which can be accomplished by several methods,summarized below. The two major classes of methods are those that use recombinant viruses and those that use naked DNA or DNA complexes.
The Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine is a cancer treatment,research and education institution with six locations in the St. Louis area. Siteman is the only cancer center in Missouri and within 240 miles of St. Louis to be designated a Comprehensive Cancer Center by the National Cancer Institute (NCI). Siteman is also the only area member of the National Comprehensive Cancer Network,a nonprofit alliance of 32 cancer centers dedicated to improving the quality and effectiveness of cancer care.
Many variants of herpes simplex virus have been considered for viral therapy of cancer;the early development of these was thoroughly reviewed in the journal Cancer Gene Therapy in 2002. This page describes the most notable variants—those tested in clinical trials:G207,HSV1716,NV1020 and Talimogene laherparepvec. These attenuated versions are constructed by deleting viral genes required for infecting or replicating inside normal cells but not cancer cells,such as ICP34.5,ICP6/UL39,and ICP47.
Adenovirus varieties have been explored extensively as a viral vector for gene therapy and also as an oncolytic virus.
Lentiviral vectors in gene therapy is a method by which genes can be inserted,modified,or deleted in organisms using lentiviruses.
Ram I. Mahato is a professor and chairman of the Department of Pharmaceutical Sciences,University of Nebraska Medical Center,Omaha,United States. He was Professor of Pharmaceutical Sciences and Biomedical Engineering at the University of Tennessee Health Science Center,Memphis. He was Research Assistant Professor at the University of Utah,Senior Scientist at GeneMedicine Inc and a postdoctoral fellow at the University of Southern California,Washington University in St. Louis,and Kyoto University. He received a PhD in drug delivery from the University of Strathclyde and BS from China Pharmaceutical University. He is a CRS Fellow,AAPS Fellow,Permanent Member of BTSS/NIH Study section (2009–2013),and ASGCT Scientific Advisor.
Maurice Green was an American virologist. He is regarded as a pioneer in the study of animal viruses,in particular their role in cancer. Green founded the Institute of Molecular Virology at St. Louis University School of Medicine in the late 1950s,and later served as its chairman.
Enadenotucirev is an investigational oncolytic virus that is in clinical trials for various cancers.
A viral vector vaccine is a vaccine that uses a viral vector to deliver genetic material (DNA) that can be transcribed by the recipient's host cells as mRNA coding for a desired protein,or antigen,to elicit an immune response. As of April 2021,six viral vector vaccines,four COVID-19 vaccines and two Ebola vaccines,have been authorized for use in humans.