Expression of adenovirally delivered gene products in healing osseous tissues

被引:21
作者
Spector, JA
Mehrara, BJ
Luchs, JS
Greenwald, JA
Fagenholz, PJ
Saadeh, PB
Steinbrech, DS
Longaker, MT
机构
[1] NYU Med Ctr, Inst Reconstruct Plast Surg, Lab Dev Biol & Repair, New York, NY 10016 USA
[2] NYU Med Ctr, Dept Surg, New York, NY 10016 USA
关键词
D O I
10.1097/00000637-200044050-00011
中图分类号
R61 [外科手术学];
学科分类号
摘要
Gene therapy has moved from the promise of laboratory investigation to the reality of clinical practice in just the last decade, Various methods for delivery of genes to host cells have been developed and utilized both in vitro and in vivo. From the perspective of the plastic surgeon, gene therapy holds the promise to augment healing in clinical situations that remain difficult to treat, such as chronic wounds, osteoradionecrosis, or possibly to expedite current clinical practices, such as distraction osteogenesis. The authors chose to investigate the potential for gene therapy in osseous tissues using a replication-deficient adenovirus vector to deliver the marker transgene beta-galactosidase. An adenovirus vector is ideal for use in situations in which transgene expression is desired for only a relatively short period of time, such as wound and fracture healing. Utilizing a rat mandibular osteotomy model, they demonstrated that, using an adenoviral vector, foreign genes can be delivered in a simple fashion and can be expressed in a reliable manner within and around the osteotomy site for at least 10 days. Furthermore, there was no evidence of transfection of distant tissues associated with local application of the adenovirus vector. With this information, clinicians may now attempt to deliver osteogenic and angiogenic genes in a site-specific fashion to improve and expedite osseous healing.
引用
收藏
页码:522 / 528
页数:7
相关论文
共 42 条
[1]   Dystrophin expression in muscles of mdx mice after adenovirus-mediated in vivo gene transfer [J].
Acsadi, G ;
Lochmuller, H ;
Jani, A ;
Huard, J ;
Massie, B ;
Prescott, S ;
Simoneau, M ;
Petrof, BJ ;
Karpati, G .
HUMAN GENE THERAPY, 1996, 7 (02) :129-140
[2]  
BECK LS, 1993, J BONE MINER RES, V8, P753
[3]   Exogenous fibroblast growth factors-1 and -2 do not accelerate fracture healing in the rabbit [J].
Bland, YS ;
Critchlow, MA ;
Ashhurst, DE .
ACTA ORTHOPAEDICA SCANDINAVICA, 1995, 66 (06) :543-548
[4]  
BOLANDER ME, 1992, P SOC EXP BIOL MED, V200, P165
[5]  
Bostrom MPG, 1998, CLIN ORTHOP RELAT R, pS274
[6]   Expression of bone morphogenetic proteins in fracture healing [J].
Bostrom, MPG .
CLINICAL ORTHOPAEDICS AND RELATED RESEARCH, 1998, (355) :S116-S123
[7]   Transforming growth factor beta in fracture repair [J].
Bostrom, MPG ;
Asnis, P .
CLINICAL ORTHOPAEDICS AND RELATED RESEARCH, 1998, (355) :S124-S131
[8]   ADMINISTRATION OF AN ADENOVIRUS CONTAINING THE HUMAN CFTR CDNA TO THE RESPIRATORY-TRACT OF INDIVIDUALS WITH CYSTIC-FIBROSIS [J].
CRYSTAL, RG ;
MCELVANEY, NG ;
ROSENFELD, MA ;
CHU, CS ;
MASTRANGELI, A ;
HAY, JG ;
BRODY, SL ;
JAFFE, HA ;
EISSA, NT ;
DANEL, C .
NATURE GENETICS, 1994, 8 (01) :42-51
[9]   TRANSFER OF GENES TO HUMANS - EARLY LESSONS AND OBSTACLES TO SUCCESS [J].
CRYSTAL, RG .
SCIENCE, 1995, 270 (5235) :404-410
[10]  
DELUSTRO F, 1990, CLIN ORTHOP RELAT R, P263