Gene delivery to bone.
Gene delivery to bone.
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DOI：
10.1016/j.addr.2012.03.013
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发表时间：
2012-09
影响因子：
16.1
通讯作者：
Evans, C. H.
中科院分区：
文献类型：
--
作者：
Evans, C. H.
关键词：
基因传递到骨是有用的实验工具，并作为一个潜在的治疗策略。其相对于蛋白质递送的优势之一是真正加工的新生蛋白质的定向、持续和调节表达的潜力。虽然尚未启动临床试验，但有大量临床前文献记录了基因成功转移到骨及其骨内表达。衍生自腺病毒、逆转录病毒和慢病毒的重组载体以及非病毒载体已用于此目的。已经探索了离体和体内策略，包括基因活化基质。离体递送通常采用间充质干细胞（MSC），部分原因是它们分化成骨细胞的能力。MSC还具有在全身给药后归巢至骨的潜力，这可以作为以播散方式递送转基因的有用方式，用于治疗影响整个骨骼的疾病，如骨质疏松症或骨生成障碍。成骨转基因的局部递送，特别是那些编码骨形态发生蛋白的转基因，在许多需要再生骨的应用中显示出巨大的前景。这些包括愈合长骨和颅骨中的大段缺损，以及脊柱融合和治疗缺血性坏死。
Gene delivery to bone is useful both as an experimental tool and as a potential therapeutic strategy. Among its advantages over protein delivery are the potential for directed, sustained and regulated expression of authentically processed, nascent proteins. Although no clinical trials have been initiated, there is a substantial pre-clinical literature documenting the successful transfer of genes to bone, and their intraosseous expression. Recombinant vectors derived from adenovirus, retrovirus and lentivirus, as well as non-viral vectors, have been used for this purpose. Both ex vivo and in vivo strategies, including gene-activated matrices, have been explored. Ex vivo delivery has often employed mesenchymal stem cells (MSCs), partly because of their ability to differentiate into osteoblasts. MSCs also have the potential to home to bone after systemic administration, which could serve as a useful way to deliver transgenes in a disseminated fashion for the treatment of diseases affecting the whole skeleton, such as osteoporosis or osteogenesis imperfecta. Local delivery of osteogenic transgenes, particularly those encoding bone morphogenetic proteins, has shown great promise in a number of applications where it is necessary to regenerate bone. These include healing large segmental defects in long bones and the cranium, as well as spinal fusion and treating avascular necrosis.
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