学科主题临床医学
Delivery of cell-penetrating peptide-peptide nucleic acid conjugates by assembly on an oligonucleotide scaffold
Zhao, Xing-Liang1; Chen, Bi-Cheng2,3; Han, Jin-Chao1; Wei, Lai1; Pan, Xiao-Ben1
刊名SCIENTIFIC REPORTS
2015-11-27
DOI10.1038/srep17640
5
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Multidisciplinary Sciences
研究领域[WOS]Science & Technology - Other Topics
关键词[WOS]HEPATITIS-B-VIRUS ; CHROMOSOMAL DNA ; SPLICING CORRECTION ; GENE-EXPRESSION ; TAT PEPTIDE ; HIV-TAT ; PNA ; TRANSCRIPTION ; RECOGNITION ; ANTISENSE
英文摘要

Delivery to intracellular target sites is still one of the main obstacles in the development of peptide nucleic acids (PNAs) as antisense-antigene therapeutics. Here, we designed a self-assembled oligonucleotide scaffold that included a central complementary region for self-assembly and lateral regions complementing the PNAs. Assembly of cell-penetrating peptide (CPP)-PNAs on the scaffold significantly promoted endocytosis of PNAs by at least 10-fold in cell cultures, particularly for scaffolds in which the central complementary region was assembled by poly(guanine) and poly(cytosine). The antisense activity of CPP-PNAs increased by assembly on the scaffold and was further enhanced after co-assembly with endosomolytic peptide (EP)-PNA. This synergistic effect was also observed following the assembly of antigene CPP-PNAs\EP-PNAs on the scaffold. However, antigene activity was only observed by targeting episomal viral DNA or transfected plasmids, but not the chromosome in the cell cultures. In conclusion, assembly on oligonucleotide scaffolds significantly enhanced the antisense-antigene activity of PNAs by promoting endocytosis and endosomal escape. This oligonucleotide scaffold provided a simple strategy for assembly of multiple functional peptide-PNA conjugates, expanding the applications of PNAs and demonstrating the potential of PNAs as antiviral therapeutics.

语种英语
WOS记录号WOS:000365477500001
引用统计
被引频次:5[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/63204
专题北京大学第二临床医学院_北京大学肝病研究所
作者单位1.Peking Univ, Peking Univ Peoples Hosp, Inst Hepatol, Beijing Key Lab Hepatitis & Immunotherapy Liver D, Beijing 100044, Peoples R China
2.Wenzhou Key Lab Surg, Zhejiang Prov Top Key Discipline Surg, Wenzhou 325200, Peoples R China
3.Wenzhou Med Univ, Affiliated Hosp 1, Dept Surg, Wenzhou 325200, Peoples R China
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GB/T 7714
Zhao, Xing-Liang,Chen, Bi-Cheng,Han, Jin-Chao,et al. Delivery of cell-penetrating peptide-peptide nucleic acid conjugates by assembly on an oligonucleotide scaffold[J]. SCIENTIFIC REPORTS,2015,5.
APA Zhao, Xing-Liang,Chen, Bi-Cheng,Han, Jin-Chao,Wei, Lai,&Pan, Xiao-Ben.(2015).Delivery of cell-penetrating peptide-peptide nucleic acid conjugates by assembly on an oligonucleotide scaffold.SCIENTIFIC REPORTS,5.
MLA Zhao, Xing-Liang,et al."Delivery of cell-penetrating peptide-peptide nucleic acid conjugates by assembly on an oligonucleotide scaffold".SCIENTIFIC REPORTS 5(2015).
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