David T. Curiel, M.D., Ph.D.

Professor
Radiation Oncology
Cancer Biology

Molecular Microbiology and Microbial Pathogenesis Program
Molecular Genetics and Genomics Program
Immunology Program
Developmental, Regenerative and Stem Cell Biology Program

  • 314-286-2199

  • 314-362-9338

  • 314-362-9790

  • 8224

  • 4950 Children`s Place, Ste 10130

  • dcuriel@radonc.wustl.edu

  • Adenovirus, virotherapy, virus, cancer, gene therapy, vaccine

  • To address the central mandate of gene therapy we engineer adenovirus tropism to allow the achievement of effective gene delivery

Research Abstract:

Human gene therapy offers unprecedented opportunities to achieve targeted therapy for a range of inherited and acquired disorders. Recent human trials have achieved spectacular cures in contexts whereby available gene transfer vectors could address the central mandate of effective gene delivery. Field advancements for gene therapy will thus clearly be linked to the development of vectors capable of efficient and specific gene delivery to target cells.

We are addressing these key issues via the employment of human adenovirus (Ad) as a vector vehicle. Genetic engineering of recombinant Ad has allowed dramatic gains in vector efficacy. Validation of vector gains in stringent model systems has allowed the translation of our novel Ad vectors into the context of pivotal human trials for a range of inherited and acquired disorders.
We are also exploring the utilities of gene editing to facilitate long term gene expression via adenoviral vectors. This new vector capacity now allows us to apply Ad for the wider context of corrective gene therapy for inherited genetic disease. Our work in this area is carried out via our membership within the NIH Common Fund’s Somatic Cell Genome Editing (SCGE) program.

Selected Publications:

Stephens CJ, Lauron EJ, Kashentseva E, Lu ZH, Yokoyama WM, Curiel DT. Long-term correction of hemophilia B using adenoviral delivery of CRISPR/Cas9. Journal of Controlled Release. 2019;298:128-41. doi: 10.1016/j.jconrel.2019.02.009. PubMed PMID: 30771412.

Stephens CJ, Kashentseva E, Everett W, Kaliberova L, Curiel DT. Targeted in vivo knock-in of human alpha-1-antitrypsin cDNA using adenoviral delivery of CRISPR/Cas9. Gene Therapy. 2018;25(2):139-56. doi: 10.1038/s41434-018-0003-1. PubMed PMID: 29588497; PMCID: PMC5919923.

Buggio M, Towe C, Annan A, Kaliberov S, Lu ZH, Stephens C, Arbeit JM, Curiel DT. Pulmonary vasculature directed adenovirus increases epithelial lining fluid alpha-1 antitrypsin levels. The Journal of Gene Medicine. 2016;18(1-3):38-44. doi: 10.1002/jgm.2874. PubMed PMID: 26825735.

van Erp EA, Kaliberova LN, Kaliberov SA, Curiel DT. Retargeted oncolytic adenovirus displaying a single variable domain of camelid heavy-chain-only antibody in a fiber protein. Molecular Therapy Oncolytics. 2015;2:15001. doi: 10.1038/mto.2015.1. PubMed PMID: 27119101; PMCID: 4782946.

Dmitriev IP, Kashentseva EA, Kim KH, Matthews QL, Krieger SS, Parry JJ, Nguyen KN, Akers WJ, Achilefu S, Rogers BE, Alvarez RD, Curiel DT. Monitoring of biodistribution and persistence of conditionally replicative adenovirus in a murine model of ovarian cancer using capsid-incorporated mCherry and expression of human somatostatin receptor subtype 2 gene. Mol Imaging. 2014;13. doi: 10.2310/7290.2014.00024. PubMed PMID: 25249483.

Kaliberov SA, Kaliberova LN, Buggio M, Tremblay JM, Shoemaker CB, Curiel DT. Adenoviral targeting using genetically incorporated camelid single variable domains. Laboratory Investigation; a journal of technical methods and pathology. 2014;94(8):893-905. doi: 10.1038/labinvest.2014.82. PubMed PMID: 24933423; PMCID: 4157633.

Last Updated: 10/11/2019 2:32:31 PM

Employment of adenovirus to accomplish in vivo gene editing for genetic correction of inherited genetic disorders.
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