A fusion of minicircle DNA and nanoparticle delivery technologies facilitates therapeutic genetic engineering of autologous canine olfactory mucosal cells.
A fusion of minicircle DNA and nanoparticle delivery technologies facilitates therapeutic genetic engineering of autologous canine olfactory mucosal cells.
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小环 DNA 和纳米颗粒递送技术的融合促进了自体犬嗅粘膜细胞的治疗性基因工程。
DOI：
10.1039/c7nr00811b
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发表时间：
2017
期刊：
影响因子：
6.7
通讯作者：
Delaney AM
中科院分区：
文献类型：
--
作者：
Delaney AM
嗅鞘细胞(OECs)移植到损伤脊髓后可促进轴突再生，改善运动功能。最近的一项临床试验表明，自体嗅鞘细胞移植后，患有脊髓损伤的家犬的运动功能得到了改善。它们在犬身上的效用为人类翻译提供了希望，因为狗在临床管理和遗传/环境变异方面与人类相当。此外，嗅鞘细胞的自体、微创来源使其适用于人类脊柱损伤的研究。对移植人群进行基因工程可能会增强他们的治疗潜力，但在很大程度上依赖于病毒方法，这些方法在临床翻译方面有几个缺点。我们在这里提出了第一个证据，即部署了外加磁场和先进的DNA微环载体的磁性颗粒可以安全地生物工程嗅鞘细胞分泌一种关键的神经营养因子，其效率接近病毒载体。我们认为，我们的替代方法为增强的临床细胞疗法的交付提供了很高的翻译潜力。
Olfactory ensheathing cells (OECs) promote axonal regeneration and improve locomotor function when transplanted into the injured spinal cord. A recent clinical trial demonstrated improved motor function in domestic dogs with spinal injury following autologous OEC transplantation. Their utility in canines offers promise for human translation, as dogs are comparable to humans in terms of clinical management and genetic/environmental variation. Moreover, the autologous, minimally invasive derivation of OECs makes them viable for human spinal injury investigation. Genetic engineering of transplant populations may augment their therapeutic potential, but relies heavily on viral methods which have several drawbacks for clinical translation. We present here the first proof that magnetic particles deployed with applied magnetic fields and advanced DNA minicircle vectors can safely bioengineer OECs to secrete a key neurotrophic factor, with an efficiency approaching that of viral vectors. We suggest that our alternative approach offers high translational potential for the delivery of augmented clinical cell therapies.
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