Hyaluronic acid-binding insulin-like growth factor-1: Creation of a gene encoding a bifunctional fusion protein.
Hyaluronic acid-binding insulin-like growth factor-1: Creation of a gene encoding a bifunctional fusion protein.
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DOI：
10.1007/s11033-020-06034-w
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发表时间：
2020-12
影响因子：
2.8
通讯作者：
Trippel SB
中科院分区：
文献类型：
--
作者：
Shi S;Wang C;Trippel SB
软骨生长因子是一种很有前途的关节软骨修复治疗药物。实现这一承诺的持续障碍是在需要修复的软骨损伤区域内应用和保留生长因子的能力有限。目前的治疗方法成功地递送细胞和/或基质，但生长因子容易扩散到关节间隙，然后从关节中流失。为了解决这个问题，我们创造了一个新的基因，编码由基质结合域和生长因子组成的双功能融合蛋白。该基因编码软骨基质分子的透明质酸结合区versican和软骨生长因子胰岛素样生长因子-1 （IGF-1）。我们将该基因以腺相关病毒为基础的质粒载体传递到关节软骨细胞。细胞合成并分泌融合蛋白基因产物。融合蛋白与透明质酸结合，并保留了IGF-1对软骨细胞的合成代谢和有丝分裂作用。这项概念验证研究表明，双功能融合蛋白与软骨细胞和基于透明质酸的递送载体协同作用，可以作为关节内治疗来帮助实现关节软骨修复。
Chondrogenic growth factors are promising therapeutic agents for articular cartilage repair. A persistent impediment to fulfilling this promise is a limited ability to apply and retain the growth factors within the region of cartilage damage that is in need of repair. Current therapies successfully deliver cells and/or matrices, but growth factors are subject to diffusion into the joint space and then loss from the joint. To address this problem, we created a novel gene that encodes a bifunctional fusion protein comprised by a matrix binding domain and a growth factor. The gene encodes the hyaluronic acid binding region of the cartilage matrix molecule, versican, and the chondrogenic growth factor, insulin-like growth factor-1 (IGF-1). We delivered the gene in an adeno-associated virus-based plasmid vector to articular chondrocytes. The cells synthesized and secreted the fusion protein gene product. The fusion protein bound to hyaluronic acid and retained the anabolic and mitogenic actions of IGF-1 on the chondrocytes. This proof-of-concept study suggests that the bifunctional fusion protein, in concert with chondrocytes and a hyaluronic acid-based delivery vehicle, may serve as an intra-articular therapy to help achieve articular cartilage repair.
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作者：
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DOI：
10.1302/0301-620x.89b5.18343
发表时间：
2007-05-01
影响因子：
--
作者：
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通讯作者：
Nixon, A. J.