David Curiel, MD, PhD develops gene transfer vectors to advance the human application of gene therapy. To overcome the limited capacity of available viral vectors to deliver large genes, Dr. Curiel conceptualized an approach whereby heterologous DNA was carried on the exterior of the virus rather than configured within the parental virus genome. This design is a conceptual departure from all historical vector paradigms. This new system embodies elements of viral vectors and non-viral vector configured into a single particle. This design takes advantage of both classes of vector agents in a wide range of applied contexts, including a human clinical trial of cancer vaccination in Europe. This vector design was featured in a news item in the journal Science. In addition, this concept of derived “mosacic” vectors, now represents a legitimate sub-field within gene therapy. In addition, the “mosacic” design paradigms resulted in the Development of an Ad-AAV Chimera: Piggy Backing Vectors Through Camelids.
Dr. Curiel identified a deficiency at the primary adenoviral receptor “CAR” in human primary tumor not noted in immortalized human cell lines. The new universal recognition of “CAR deficiency” characterizing human epithelial carcinomas clearly constituted the basis of tumor cell resistance to Ad-mediated transduction, and thus failure of cancer gene therapy interventions. In addition, the spurious predictive value of immortalized human cell lines at (and their murine xenograft model derivations), suggested the need for more stringent models. Finally, the recognition of tumor cell CAR levels limiting Ad gene transfer efficacy suggested the need for Ads which embodied “CAR independent” gene transfer capacity. To this end, he endeavored a series of gene capsid modifications to alter Ad tropism to achieve CAR-independent infection of tumor cells. A number of modifications were defined that achieved this biologic goal with dramatic enhancements in Ad infectivity. These adenoviral vectors have now been applied in human clinical trials for cancer. He modified an adenovirus virotherapy agent that dramatically augmented its oncolytic potency. On this basis, the FDA has approved his application for Fast Track status for malignant gliomas.
For more information about research opportunities in Dr. Curiel’s laboratory, please contact Amanda Baker (firstname.lastname@example.org).