Introduction of specific transgenes into cells (transduction) has become a standard method used to study and define the molecular biology of both cells and whole animal systems. Recombinant gene vectors that readily transducer cells and tissues represents a critical technology for the study of rheumatic diseases. A variety of gene transfer vectors are available for the transduction of cells both in vitro and in vivo, and each type of gene vector requires specialized technology to optimize gene transfer and address production issues. Many of the techniques required for the construction, characterization and manufacture of these reagents are specialized, expensive and difficult to learn without experienced guidance. In addition, the production of these materials needs to be performed in laboratory space that has been specifically configured in order to comply with biological guidelines. The requirements for compliance with biosafety guidelines has deterred some investigators from pursuing the use of these valuable reagents. The widespread use of gene vectors by multiple investigators supported the provision of this technology in the form of a core laboratory. Recombinant gene vectors and associated technical services have been available to University of Michigan (U-M) Rheumatic Disease Core Center (RDCC) members under the Multipurpose Arthritis and Musculoskeletal Diseases Center (MAMDC) program since 1994. This current proposal is intended to maintain support for a centralized facility for the construction, purification and characterization of recombinant vectors containing genes relevant to the study of arthritis and musculoskeletal diseases for use as in vitro and in vivo gene transfer reagents. The Vector Core will provide efficient and cost effective access to both viral and non-viral gene transfer technologies including; recombinant adenovirus, recombinant MMLV retrovirus, recombinant adeno-associated virus, recombinant lentivirus and expression plasmid DNA. The quality of the reagents provided by the Vector Core will facilitate the translation of promising gene vectors into pivotal preclinical studies and Phase 1 human clinical trials.
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