GAM-rev2 - J. Bonadio ( ) Selective Genetics, Inc., 6046...

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Unformatted text preview: J. Bonadio ( ) Selective Genetics, Inc., 6046 Cornerstone Court West, Suite 107, San Diego, CA 92121, USA e-mail: jbonadio@earthlink.net Tel.: +1-858-6258414, Fax: +1-858-4556822 Abstract The first goal of this review is to describe a local plasmid gene transfer technology known as the gene activated matrix (GAM). GAM was the first gene therapy designed specifically for tissue engineering ap- plications, and the mechanism of action of plasmid gene transfer is closely tied to the normal sequence of events associated with wound healing. The normal sequence of wound healing events is stereotyped for most tissues, and one assumption has been that GAM could serve as a platform technology for local gene delivery in various tissues and organs. This hypothesis essentially has been proved: animal studies over the past 6 years have estab- lished that plasmid genes can be delivered to acutely in- jured tendon, ligament, bone, muscle, skin, and nerve. The second goal of the review is to describe the most likely first use of the technology in man, namely, treat- ment of osteoporotic hip fracture in the elderly. Although not universally appreciated, interest in osteoporotic frac- ture should grow because of epidemiological, surgical, and societal considerations. These considerations, plus the unmet clinical need associated with the current stan- J Mol Med (2000) 78:303311 DOI 10.1007/s001090000118 R E V I E W Jeffrey Bonadio Tissue engineering via local gene delivery Received: 1 February 2000 / Accepted: 8 May 2000 / Published online: 29 June 2000 Springer-Verlag 2000 J EFFREY B ONADIO was a member of the Depart- ment of Pathology, University of Michigan Medical School, until joining Selective Genet- ics, Inc., a company that he cofounded. His research inter- ests include in vivo gene trans- fer, tissue engineering, wound healing, extracellular matrix, and growth factors. These in- terests have been applied pri- marily to disorders of the mus- culoskeletal system (inherited and acquired). dard of fracture care, justify efforts to develop novel therapies for bone regeneration and repair in the elderly. Key words Wound healing Granulation tissue Growth factor Gene transfer Gene activated matrix Abbreviations GAM : Gene activated matrix PTH : Parathyroid hormone Clinical aspects of wound healing All told, the annual cost of injured or failed human tis- sues and organs runs into billions of dollars and is asso- ciated with significant loss in productive quality of life [1]. Certainly, clinical wound healing is not free of com- plications: the capacity for robust regeneration in most vertebrates may be limited to those tissues (e.g., liver, bone, and skeletal muscle) in which regeneration partial- ly recapitulates embryonic differentiation from multipo- tential stem cells. A general approach of regenerative bi- ology is to identify the cellular and molecular differences that distinguish tissue embryogenesis from wound repair (scarring) and then to recreate an embryonic (regenera-...
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GAM-rev2 - J. Bonadio ( ) Selective Genetics, Inc., 6046...

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