This application details the expansion and upgrade of a Clinical Vector Core facility at The Children's Hospital of Philadelphia (CHOP). We are proposing the construction of a new manufacturing suite and the simultaneous renovation of an existing cGMP manufacturing suite to meet the growing demand for vector to support translational research in gene therapy. This expanded, dual manufacturing suite configuration will provide complementary operational functions, enhanced capacity and flexibility, and needed capability to efficiently support all stages of clinical translational research, from pre-clinical studies to new product licensure. CHOP's vector core project directly supports translational medicine research seeking to realize the full potential of the Human Genome Project. Gene-based therapies have been in clinical trials for nearly two decades, but are only now reaching the point where clinical trials are showing efficacy, as evidenced by publications in the New England Journal of Medicine over the past year (Maguire et al (2008) N Engl J Med 358:2240);Aiuti et al (2009) N Engl J Med 360:518). These studies have shown gene therapy's safety and efficacy for a form of congenital blindness and a form of severe combined immunodeficiency disorder. This novel class of therapeutics has great potential for the treatment of many other genetic diseases, but only if responsive and productive vector core infrastructures can be built in support of promising early research. For the development of novel classes of therapeutics, the best route to success is often to start with products where the pre-clinical data are most robust, even if the market is small. Academic facilities such as CHOP's, in partnership with NIH, are able to manufacture vector at industry-level standards, but are not subject to the pressures of the marketplace. The availability of clinical-grade vectors is absolutely critical for clinical trials in gene therapy. High-quality vector is simply not readily available in the commercial sector - as such, this facility is enabling NIH-funded investigators. The strong pipeline represented by existing AAV Investigators with robust results in large animal models, coupled with clear evidence of efficacy in clinical trials already underway (vide supra), suggests that the pace of research in the field will accelerate considerably.
|Mingozzi, Federico; Anguela, Xavier M; Pavani, Giulia et al. (2013) Overcoming preexisting humoral immunity to AAV using capsid decoys. Sci Transl Med 5:194ra92|