期刊
BIOMATERIALS
卷 32, 期 10, 页码 2593-2604出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2010.11.074
关键词
Gold nanoparticle; Antisense DNA; Alternative splicing; Decoy oligonucleotides; Nucleus
资金
- Ministry of Education, Science and Technology of Korea [2009-0066379, 2009-0071807, 2009-0093821]
- National Research Foundation of Korea [2009-0071807, 2009-0066379] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
The development of a method that can efficiently deliver nucleic acids into the nucleus of living systems remains one of the key challenges for experimental and therapeutic use of nonbiological gene delivery agents. In the current study, we demonstrate a functionalized gold nanoparticle (AuNP) that can serve as a universal carrier for the delivery of DNA oligonucleotides (oligos) into the nucleus. We designed various types of DNA oligos to redirect alternative splicing of pre-mRNAs, such as MCL-1 and BCL-6, and to sequester transcriptional factors, including estrogen receptor a and p53. We successfully delivered the oligos into the nucleus, resulting in the targeted effects. In addition, injection of the antisense DNAs into a xenograft tumor in a mouse model system resulted in inhibited development of the tumor by redirecting the alternative splicing of the pre-mRNA. Our findings show that these nanoconjugates efficiently load and deliver antisense DNAs to redirect gene splicing or double-stranded DNAs to decoy gene transcription by transcriptional factors into mammalian cells and in vivo animals. Therefore, our lego-like AuNP gene delivery system can be used universally to control different biological processes by modulating nuclear gene expression events in living systems. (C) 2010 Elsevier Ltd. All rights reserved.
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