High-efficiency transduction of spinal cord motor neurons by intrauterine delivery of integration-deficient lentiviral vectors.
High-efficiency transduction of spinal cord motor neurons by intrauterine delivery of integration-deficient lentiviral vectors.
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DOI：
10.1016/j.jconrel.2017.12.029
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发表时间：
2018-03-10
期刊：
影响因子：
--
通讯作者：
Yáñez-Muñoz RJ
中科院分区：
文献类型：
--
作者：
Ahmed SG;Waddington SN;Boza-Morán MG;Yáñez-Muñoz RJ
整合缺陷慢病毒载体（idlv）是一种很有前途的基因传递工具，它保留了标准慢病毒载体的高转导效率，但不能作为原病毒整合，而是转化为外环。这些突变是代谢稳定的，支持转基因在非分裂细胞中的长期表达，显示出插入突变的风险降低。我们开展了一项广泛的研究，比较不同包膜（水疱性口炎、狂犬病、莫克拉病毒和罗斯河病毒包膜）和自互补腺相关病毒载体血清型9 （scAAV-9）在脊髓组织内注射小鼠胚胎后的转导效率（E16）。我们的研究结果表明，无论包膜假型如何，idlv都能以极高的效率转导运动神经元（MNs），而scAAV9介导约40%的脊髓运动神经元的基因传递，其他非神经元细胞也能转导。长期表达研究显示，注射后7个月基因表达稳定。综上所述，本研究的结果表明，idlv可能是子宫内脐带转导治疗策略的有效工具，例如治疗遗传性儿童早期神经退行性疾病。
Integration-deficient lentiviral vectors (IDLVs) are promising gene delivery tools that retain the high transduction efficiency of standard lentiviral vectors, yet fail to integrate as proviruses and are instead converted into episomal circles. These episomes are metabolically stable and support long-term expression of transgenes in non-dividing cells, exhibiting a decreased risk of insertional mutagenesis. We have embarked on an extensive study to compare the transduction efficiency of IDLVs pseudotyped with different envelopes (vesicular stomatitis, Rabies, Mokola and Ross River viral envelopes) and self-complementary adeno-associated viral vectors, serotype-9 (scAAV-9) in spinal cord tissues after intraspinal injection of mouse embryos (E16). Our results indicate that IDLVs can transduce motor neurons (MNs) at extremely high efficiency regardless of the envelope pseudotype while scAAV9 mediates gene delivery to ~ 40% of spinal cord motor neurons, with other non-neuronal cells also transduced. Long-term expression studies revealed stable gene expression at 7 months post-injection. Taken together, the results of this study indicate that IDLVs may be efficient tools for in utero cord transduction in therapeutic strategies such as for treatment of inherited early childhood neurodegenerative diseases.
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影响因子：
12.4
作者：
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通讯作者：
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