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1.
Targeted editing of intronic-splicing silencer enhancement of SMN2 Exon 7 inclusion by CRISPR/Case 9
LIUCHENG WU YI WANG LILI DU GUIQING JI RUI ZHOU ZEYI ZHAO JUN CHEN SHUNXING ZHU 《Biocell》2021,45(6):1501-1507
Spinal muscular atrophy (SMA) is an autosomal recessive hereditary neuromuscular disease. Exon 7 and 8 of survival of motor neuron 1 (SMN1) gene or only exon 7 homology deletion leads to the failure to produce a full-length SMN gene. The copy number of SMN2 gene with high homology of SMN1 affects the degree of disease and was the target gene for targeting therapy, in which splicing silencer in intron 7 was the key to suppress the inclusion of exon 7. In this study, we projected to use CRISPR/Case 9 for the targeted editing of intronic-splicing silencer (ISS) sequence to promote the inclusion of SMN2 exon 7 and increase the production of SMN2 full-length (FL) gene expression. It happens that there was a protospacer adjacent motif (PAM) at one end of the ISS sequence according to the design of sgRNA. The recombinant vector of sgRNA HSMN2 CRISPR/Case 9 was constructed and transfected into HEK293 cells. Sequencing results showed that the ISS sequence could be edited accurately and targeting in the predicted direction, in which deleting small fragments, inserting small amounts and mutation. Quantitative analysis of RT-PCR products by restriction enzyme of DdeI digestion showed that the FL of SMN2 increased by 8% (P < 0.05). In the primary cultured chondrocytes of SMA mice, in which sgRNA HSMN2 CRISPR/Case9 recombinant vector transfection could increase the SMN2 FL gene by 23% (P < 0.05) and significantly improve SMN protein levels (P < 0.05). CRISPR/Case 9 is an effective tool for gene editing and therapy of hereditary diseases, but it is rarely reported in the treatment of SMA diseases. This study shows that CRISPR/Case 9 was first used for the precision target of ISS sequence editing, which can effectively promote the production of SMN2 FL gene expressions, in which there was an important clinical reference value. 相似文献
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芮素文 《信息技术与信息化》2015,(3):110-111
随着科学技术的进步与发展,ASP服务基础平台的研究与开发也受到了广泛的关注。本文主要对ASP服务基础平台体系结构、ASP服务基础平台的研究与开发进行探析。 相似文献
3.
用同向啮合双螺杆挤出机对废旧轮胎全胎胶粉进行剪切脱硫,制备高性能环保再生橡胶,考察挤出工艺、补强树脂和软化剂的种类与用量对再生橡胶性能的影响。结果表明:挤出最佳工艺参数为机筒第1—13区温度为140/140/70/190/130/120/110/110/100/110/100/90/80℃,螺杆转速为140 r·min~(-1);与添加植物系软化剂的再生橡胶相比,添加矿物系软化剂固体无味油的再生橡胶物理性能更好;添加4份古马隆树脂作为补强剂,10份固体无味油作为软化剂,制备的再生橡胶物理性能最好。 相似文献
4.
Preoperative chemoradiation therapy (CRT) is becoming the standard treatment for patients with locally
advanced rectal cancer. However, individual differences in response to treatment range from a complete response to
complete resistance. Predicting the tumor response to radiotherapy may improve the efficacy of radiotherapy. This
review mainly summarizes recent studies about the molecular biomarkers that can predict the response to
radiotherapy in rectal cancer. These studies have indicated that the molecular markers involved in the response to
radiotherapy mainly include genes related to radiosensitivity, cancer stem cell-related markers, non-coding RNAs
(ncRNAs), single-nucleotide polymorphisms (SNPs) and gene methylation, and other factors including
carcinoembryonic antigen (CEA) level, anemia, lymphocytes, and signaling pathways. Many of these identified
markers are mainly associated with DNA repair, apoptosis, and cell cycle, but some involve unknown cell
mechanisms. We speculate that predictors of radiotherapy response may involve combinations of multiple molecular
biomarkers that may be useful for the development of individualized therapy for rectal cancer patients. 相似文献
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随着“西部大开发”等国家战略的实施以及这些地区城市建设的发展,许多公路、铁路等交通都需要源于或穿越这些岩溶洞穴地区,随即面临因岩溶洞穴的塌陷所导致的路基失稳与破坏问题。本文依托昌金高速某段的岩溶塌陷进行了数值模拟,并结合塌陷段模拟分析所得的岩土体参数对邻近未塌陷段的二个处治方案进行了处治工程效果的数值模拟分析,为方案比选提供依据,对岩溶洞穴地区道路建设具有一定的指导与借鉴意义。 相似文献
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结合工程实际,对基层二灰碎石施工的原材料、配合比设计、拌和及摊铺、成型碾压等影响基层质量的诸因素进行了分析探讨,并提出了相关对策,以保证施工质量。 相似文献
10.
以乙烯⁃醋酸乙烯酯共聚物(EVA)为原料,过氧化2⁃乙基己基叔丁酯(TBPE)为交联剂,合成了交联EVA双向形状记忆聚合物(SMP),并且考察了TBPE含量对于交联EVA性能的影响。结果表明,交联EVA的Tm和Tc随着TBPE含量的上升呈现下降的趋势,可以通过交联剂比例调节材料的驱动温度;交联EVA的形状固定率会随着TBPE含量的增加呈现下降趋势,最低达到88.83 %,而样品的形状恢复率均超过99 %,并且都具有单向和双向形状记忆功能;交联EVA也具有双向记忆性能,Ra,2W随着TBEC的含量增大而减小,Rr,2W则相反;因此,通过改变交联剂EVA的量,对于双向交联EVA的性能有较大影响。 相似文献