Adenovirus-mediated direct gene therapy with bone morphogenetic protein-2 produces bone
Adenovirus-mediated direct gene therapy with bone morphogenetic protein-2 produces bone
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DOI：
10.1016/s8756-3282(99)00086-1
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发表时间：
1999-06-01
期刊：
影响因子：
4.1
通讯作者：
Huard, J
中科院分区：
文献类型：
--
作者：
Musgrave, DS;Bosch, P;Huard, J
改善骨愈合的需要渗透到骨科手术的学科中。骨形态发生蛋白（BMPs）能够诱导异位和原位骨形成，然而，理想的方法来传递BMPs仍然未知。基因疗法递送BMP提供了优于植入重组BMP蛋白的几个理论优势，包括持续的BMP递送和消除对异物载体的需要。构建了携带rhBMP-2基因的复制缺陷型腺病毒载体（AdBMP-2）。直接体内基因治疗方法应用于免疫缺陷和免疫功能正常的动物，以产生肌内骨，早在注射后2周，放射照相和组织学分析显示含有成熟骨髓元素的放射致密骨，腺病毒介导的标记基因（β-半乳糖苷酶）递送到对照动物中不产生骨，但指示用AdBMP-2载体转导的细胞。此外，免疫缺陷和免疫活性动物之间的比较说明了免疫应答的程度和意义。基因治疗提供BMP-2有无数潜在的临床应用，从骨缺损愈合关节置换假体稳定。这项研究是第一个建立体内基因治疗的可行性，以提供活性BMP-2和产生骨。(Bone 24：541-547; 1999）（C）1999，Elsevier Science Inc. All rights reserved.
The need to improve bone healing permeates the discipline of orthopedic surgery. Bone morphogenetic proteins (BMPs) are capable of inducing ectopic and orthotopic bone formation, However, the ideal approach with which to deliver BMPs remains unknown. Gene therapy to deliver BMPs offers several theoretical advantages over implantation of a recombinant BMP protein, including persistent BMP delivery and eliminating the need for a foreign body carrier. A replication defective adenoviral vector was constructed to carry the rhBMP-2 gene (AdBMP-2). The direct in vivo gene therapy approach was applied in both immunodeficient and immunocompetent animals to produce intramuscular bone as early as 2 weeks following injection, Radiographic and histologic analysis revealed radiodense bone containing mature bone marrow elements, Adenovirus-mediated delivery of a marker gene (beta-galactosidase) into control animals produced no bone but indicated the cells transduced with the AdBMP-2 vector. Furthermore, comparisons between immunodeficient and immunocompetent animals illustrated the magnitude and significance of the immune response. Gene therapy to deliver BMP-2 has innumerable potential clinical applications from bone defect healing to joint replacement prosthesis stabilization. This study is the first to establish the feasibility of in vivo gene therapy to deliver active BMP-2 and produce bone. (Bone 24:541-547; 1999) (C) 1999 by Elsevier Science Inc. All rights reserved.