Non-viral Gene Delivery Methods for Bone and Joints.
Non-viral Gene Delivery Methods for Bone and Joints.
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DOI：
10.3389/fbioe.2020.598466
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发表时间：
2020
影响因子：
5.7
通讯作者：
Purmessur D
中科院分区：
文献类型：
--
作者：
Gantenbein B;Tang S;Guerrero J;Higuita-Castro N;Salazar-Puerta AI;Croft AS;Gazdhar A;Purmessur D
病毒载体的基因传递效率很高，这取决于载体的类型。然而，病毒传递带来了严重的安全问题，如低效/不可预测的重新编程结果、基因组整合以及不必要的免疫反应和毒性。因此，非病毒基因递送方法更适合于翻译，因为这些方法允许更安全的基因递送，并可以在体内、体外和体外瞬时调节基因表达。根据目前的研究，这些技术的效率似乎更有限，但它们对临床翻译很有吸引力。本文综述了骨科的最新进展，主要针对的是来自肌肉骨骼装置的骨和关节。结缔组织是已知的愈合能力较差且细胞密度相对较低的组织，即关节软骨、骨和间盘(IVD)，最近采取了几种方法。我们简要概述了现有的技术，使用纳米球/工程囊泡、脂质体和体内电穿孔。在这里，将讨论传递microRNA(MiRNA)、沉默RNA(SiRNA)和DNA质粒。最近的研究旨在促进这些组织的再生，涉及骨形态发生蛋白(BMPs)的传递，如BMP2，以促进骨愈合。对于关节软骨/骨软骨交界处，非病毒方法主要集中于靶向软骨细胞或MSCs的组织工程方法。对于IVD，生长因子如GDF5或GDF6或发育转录因子如brachyury或FOXF1似乎具有很高的临床价值。然而，最有效的基因转移方法仍然是难以捉摸的，因为一些临床前研究已经报道了许多不同的非病毒方法，这些技术的临床翻译仍然需要验证。在这里，我们讨论了非病毒方法应用于骨和关节，并提出了有希望在临床上应用的方法。
Viral carrier transport efficiency of gene delivery is high, depending on the type of vector. However, viral delivery poses significant safety concerns such as inefficient/unpredictable reprogramming outcomes, genomic integration, as well as unwarranted immune responses and toxicity. Thus, non-viral gene delivery methods are more feasible for translation as these allow safer delivery of genes and can modulate gene expression transiently both in vivo, ex vivo, and in vitro. Based on current studies, the efficiency of these technologies appears to be more limited, but they are appealing for clinical translation. This review presents a summary of recent advancements in orthopedics, where primarily bone and joints from the musculoskeletal apparatus were targeted. In connective tissues, which are known to have a poor healing capacity, and have a relatively low cell-density, i.e., articular cartilage, bone, and the intervertebral disk (IVD) several approaches have recently been undertaken. We provide a brief overview of the existing technologies, using nano-spheres/engineered vesicles, lipofection, and in vivo electroporation. Here, delivery for microRNA (miRNA), and silencing RNA (siRNA) and DNA plasmids will be discussed. Recent studies will be summarized that aimed to improve regeneration of these tissues, involving the delivery of bone morphogenic proteins (BMPs), such as BMP2 for improvement of bone healing. For articular cartilage/osteochondral junction, non-viral methods concentrate on targeted delivery to chondrocytes or MSCs for tissue engineering-based approaches. For the IVD, growth factors such as GDF5 or GDF6 or developmental transcription factors such as Brachyury or FOXF1 seem to be of high clinical interest. However, the most efficient method of gene transfer is still elusive, as several preclinical studies have reported many different non-viral methods and clinical translation of these techniques still needs to be validated. Here we discuss the non-viral methods applied for bone and joint and propose methods that can be promising in clinical use.
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影响因子：
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作者：
Ali, Omar A.;Mooney, David J.
通讯作者：
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