The Research Institute at Nationwide Children's Hospital - K. Reed Clark, Ph.D. Profile
K. Reed Clark, Ph.D.
photo of K. Reed Clark, Ph.D.

BIOGRAPHY

STAFF INFO

PUBLICATIONS
Center for Gene Therapy

PRINCIPAL INVESTIGATOR

K.Reed.Clark@
nationwidechildrens.org

The Research Institute at Nationwide Children's Hospital
700 Childrens Drive
Columbus, OH 43205
p: 614.722.5615 | f: 614.722.3273

Education
1992      Ph.D.      Molecular Genetics      The Ohio State University, Columbus, OH
1984      B.S.      Genetics      The Ohio State University, Columbus, OH


Professional Experience
2005- PRES Associate Center Director, Center for Gene Therapy, The Research Institute at Nationwide Children's Hospital, Columbus, OH
2002- PRES Associate Professor, Department of Pediatrics, Division of Molecular Medicine, The Ohio State University, Columbus, OH
1997- PRES Director, Viral Vector Core Facility, The Research Institute at Nationwide Children's Hospital, Columbus, OH
1997- PRES Assistant Professor, Department of Pediatrics, Division of Molecular Medicine, The Ohio State University, Columbus, OH
1997- 2002 Assistant Professor , Department of Pediatrics and Molecular Virology and Molecular Genetics, Division of Molecular Medicine, The Ohio State University, Columbus, OH
1992- 1996 Post-Doctoral Fellow, Laboratory of Philip R. Johnson, M.D., Department of Pediatrics, Division of Molecular Medicine, The Ohio State University, Columbus, OH
1988- 1990 Lecturer, Introductory Genetics, The Ohio State University, Columbus, OH
1986- 1990 Graduate Teaching Assistant in Molecular Genetics, The Ohio State University, Columbus, OH


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Research Interests

My laboratory is interested in utilizing recombinant adeno-associated virus mediated (rAAV) gene transfer to develop meaningful treatments for genetic and infectious diseases.  Current research focuses on three principle areas: (i) use of antibody gene transfer as a means to augment host immunity; (ii) use of RNA based anti-sense therapeutics to achieve exon-skipping of the dystrophin gene for treatment of DMD; and (iii) development of scalable rAAV production platforms using novel AAV serotypes to support clinical trials.  Antibody gene transfer:  The focus of this project is to develop AAV delivery vectors that efficiently express antibodies of predetermined specificity within host tissue.  Because of the inherent flexibility of this system, light and heavy chain antibody genes can be incorporated into a single rAAV vector, and the antibody-expressing vector can then be used to transduce target tissue in vivo (muscle, liver, and pleural cavity).  This in turn, leads to sustained expression of biologically active antibody molecules in the circulation.  We have shown that human anti-HIV-1 monoclonal antibodies can be expressed in mice and non-human primates – endowing the host with anti-HIV-1 in vitro neutralization activity.  Thus, this approach allows for predetermination of antibody affinity and specificity prior to "immunization", and avoids the need for an active humoral immune response.  Beyond the current application for HIV-1 infection, this strategy might be useful for other situations where antibodies with predetermined specificities need to be delivered in vivo.  Currently, we are evaluating methods to further augment in vivo levels using various AAV serotypes and routes of delivery.  Exon-Skipping:  The goal of this project is to develop a meaningful therapy to treat muscular dystrophy caused by mutations within the dystrophin gene that ablate the reading frame.  We have constructed several rAAV gene transfer vectors that express anti-sense splice sequences linked to a modified U7 small nuclear RNA (snRNA).  Expression of these RNAs block inclusion of the mutated dystrophin exon into the mRNA transcript.  This results in the generation of a functional (albeit slightly smaller) dystrophin mRNA and protein product.  Currently, we are evaluating exonic splice enhancers (ESEs) as potential targets for efficient skipping and methods of vascular delivery to the muscles of the lower limbs.  Lastly, we are developing scalable production and purification methods using stable cell lines and transient transfection technologies for the production of multiple AAV serotypes (1-9).  Current research has focused on developing a cGMP “friendly” approach to large-scale production that can be transitioned into our production facility upon its completion.