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Modulation of biological processes in the nucleus by delivery of DNA oligonucleotides conjugated with gold nanoparticles

Paper ID Volume ID Publish Year Pages File Format Full-Text
8105 577 2011 12 PDF Available
Title
Modulation of biological processes in the nucleus by delivery of DNA oligonucleotides conjugated with gold nanoparticles
Abstract

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 α 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.

Keywords
Gold nanoparticle; Antisense DNA; Alternative splicing; Decoy oligonucleotides; Nucleus
First Page Preview
Modulation of biological processes in the nucleus by delivery of DNA oligonucleotides conjugated with gold nanoparticles
Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 32, Issue 10, April 2011, Pages 2593–2604
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering